Development of a scalable synthesis of (S)-3-fluoromethyl-γ- butyrolactone, building block for Carmegliptin's Lactam moiety

Organic Process Research and Development

Volumn 15, Issue 3, 2011, Pages 515-526

  Adam, Jean Michel ^a   Foricher, Joseph ^a   Hanlon, Steven ^a   Lohri, Bruno ^a   Moine, Gérard ^a   Schmid, Rudolf ^a   Stahr, Helmut ^a   Weber, Martin ^a   Wirz, Beat ^a   Zutter, Ulrich ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BUILDING BLOCKES; BUTYROLACTONES; FURTHER DEVELOPMENT; SCALABLE SYNTHESIS; STEREO-SELECTIVE; TERT-BUTYL GLYCIDYL ETHER;

HYDROGENATION;

ETHERS;

EID: 79957496940     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op200019k     Document Type: Article

References (66)

1. Mattei, P.; Böhringer, M.; Di Giorgio, P.; Fischer, H.; Hennig, M.; Huwyler, J.; Koçer, B.; Kuhn, B.; Loeffler, B. M.; MacDonald, A.; Narquizian, R.; Rauber, E.; Sebokova, E.; Sprecher, U. Bioorg. Med. Chem. Lett. 2010, 20, 1109
2. Böhringer, M.; Fischer, H.; Hennig, M.; Hunziker, D.; Huwyler, J.; Kuhn, B.; Loeffler, B. M.; Luebbers, T.; Mattei, M.; Narquizian, R.; Sebokova, E.; Sprecher, U.; Wessel, H. P. Bioorg. Med. Chem. Lett. 2010, 20, 1106
3. Abrecht, S.; Adam, J.-M.; Bromberger, U.; Diodone, R.; Fettes, A.; Fischer, R.; Göckel, V.; Hildbrand, S.; Moine, G.; Weber, M. Org. Process Res. Dev. 2011, DOI: 10.1021/op2000207.
4. See also: Abrecht, S.; Adam, J.-M.; Fettes, A.; Foricher, J.; Lohri, B.; Mattei, P.; Moine, G.; Schmid, R.; Zutter, U. (F. Hoffmann-La Roche AG). PCT Int. Appl. WO 2006/125728 A1, 2006.
5. Zutter, U. (F. Hoffmann-La Roche Inc.). U.S. Pat. Appl. Publ. U.S. 2008/108816 A1, 2008.
6. The Horner-Wadsworth-Emmons route to hydroxymethyl butenolide 6 is known; see: Gadir, S. A.; Smith, Y.; Taha, A. A.; Thaller, V. J. Chem. Res., Synop. 1986, 222
7. Harrison, T.; Myers, P. L.; Pattenden, G. Tetrahedron 1989, 45, 5247
8. Lattmann, E.; Hoffmann, H. M. R. Synthesis 1996, 155
9. Balasubramaniam, R. P.; Moss, D. K.; Wyatt, J. K.; Spence, J. D.; Gee, A.; Nantz, M. H. Tetrahedron 1997, 53, 7429
10. Crawforth, J. M.; Fawcett, J.; Rawlings, B. J. J. Chem. Soc., Perkin Trans. 1 1998, 1721
11. See e.g.: Mori, K.; Yamane, K. Tetrahedron 1982, 38, 2919
12. Mori, K.; Chiba, N. Liebigs Ann. Chem 1989, 957 A sample of (R)- 7 prepared in-house by the Evans route suffered from ∼90% racemization upon standing at ambient temperature for three weeks; Dr. P. Mattei, personal communication.
13. Ohta, T.; Miyake, T.; Seido, N.; Kumobayashi, H.; Takaya, H. J. Org. Chem. 1995, 60, 357
14. Kamlage, S.; Sefkow, M.; Zimmermann, N.; Peter, M. G. Synlett 2002, 77
15. Bronze-Uhle, E. S.; de Sairre, M. I.; Donate, P. M.; Frederico, D. J. Mol. Catal. A: Chem. 2006, 259, 103
16. Hughes, G.; Kimura, M.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 11253
17. Geiger, C.; Kreitmeier, P.; Reiser, O. Adv. Synth. Catal. 2005, 347, 249
18. See e.g. Takabe, K.; Tanaka, M.; Sugimoto, M.; Yamada, T.; Yoda, H. Tetrahedron: Asymmetry 1992, 3, 1385
19. Asymmetric hydrogenation of hydroxymethyl butenolide 6 was reported to lead to material of very low ee, likely due to the propensity of the optically active product 7 to racemize (cf. reference 8c).
20. Commercial material was used, or the ylide was prepared and isolated from [(ethoxycarbonyl)methyl]triphenylphosphonium bromide in a NaOH/DCM two-phase system.
21. 1,3-Dihydroxyacetone (12) in substance exists mainly in the dimeric hemiacetal form unless freshly distilled; see: Fischer, H. O. L.; Mildbrand, H. Ber. Dtsch. Chem. Ges. B 1924, 57B, 707
22. Davies, L. Bioorg. Chem. 1973, 2, 197
23. Yoda, H.; Mizutani, M.; Takabe, K. Synlett 1998, 855 The monomer/dimer ratio had no influence on the reaction.
24. 4 in MeOH) was less selective and led to material that was difficult to purify by distillation or crystallization.
25. 2 t- Bu and ester cleavage-cyclization with 0.25 M HCl in methanol. Hydroxymethyl butenolide 6 was obtained in 73% yield over two steps after chromatography which proved inevitable.
26. Singh, R. P.; Shreeve, J. M. Synthesis 2002, 2561 and references cited therein
27. Yin, J.; Zarkowsky, D. S.; Thomas, D. W.; Zhao, M. M.; Huffman, M. A. Org. Lett. 2004, 6, 1465
28. For a review see: Haufe, G. J. Fluorine Chem. 2004, 125, 875
29. Van Hijfte, L.; Heydt, V.; Kolb, M. Tetrahedron Lett. 1993, 34, 4793
30. The primary alcohol rac- 16 is slightly less volatile than the secondary alcohol rac- 15. Pure samples of rac- 15 and rac- 16 were obtained by chromatography.
31. Further polar solvents such as DMF, DMA, NMP, DMPU, and DMSO proved poor in terms of chemoselectivity and yields and/or rates.
32. 3N•3HF, see: Giudicelli, M. B.; Picq, D.; Veyron, B. Tetrahedron Lett. 1990, 31, 6527
33. Chou, T. S.; Becke, L. M.; O'Toole, J. C.; Carr, M. A.; Parker, B. E. Tetrahedron Lett. 1996, 37, 17
34. 4 necessitated an aqueous workup and exhaustive extraction of 19 with ethyl acetate leading to high volume factors.
35. 3 led to unsatisfactory conversions and/or yields.
36. More than 250 strains produced the undesired enantiomer (R)- 3, many with 100% conversion and ee values >98%. Screenings were performed in a 24 deep-well format at 0.1% w/v substrate concentration.
37. Iridium catalysts in a short screening afforded only low conversions and enantioselectivities.
38. Benincori, T.; Cesarotti, E.; Piccolo, O.; Sannicoló, F. J. Org. Chem. 2000, 65, 2043
39. Antognazza, P.; Benincori, T.; Brenna, E.; Cesarotti, E.; Sannicoló, F.; Trimarco, L. (Italfarmaco Sud S.P.A.). PCT Int. Appl. WO 96/01831 A1, 1996.
40. Preformed Ru catalysts were prepared as described; cf.: Heiser, B.; Broger, E. A.; Crameri, Y. Tetrahedron: Asymmetry 1991, 2, 51
41. Cereghetti, M.; Foricher, J.; Heiser, B.; Schmid, R. (F. Hoffmann-La Roche Inc.). U.S. Patent 5,488,172, 1996.
42. 2(COD)] and the bisphosphine ligand in the presence of the starting material 13 and MeOH (40 °C, 2 h). Only marginal ee differences were observed in cases where both the preformed and the in situ prepared catalyst were evaluated.
43. 2, 40 °C, 20 h, DCM) provided 92% ee, equal to the ee obtained for 13.
44. Banfi, L.; Basso, A.; Guanti, G.; Zannetti, M. T. Tetrahedron: Asymmetry 1997, 8, 4079
45. Yoshida, Y.; Sakakura, Y.; Aso, N.; Okada, S.; Tanabe, Y. Tetrahedron 1999, 55, 2183
46. For an independent synthesis based on a microbial Bayer-Villiger oxidation of 3-benzyloxy-cyclobutanone see: Mazzini, C.; Lebetron, J.; Alphand, V.; Furstoss., R. J. Org. Chem. 1997, 62, 5215
47. For a synthesis of (R)- 27 starting from (R)-paraconic acid ((R)- 11) see: Mori, K. Tetrahedron 1983, 39, 3107
48. For the preparation of optically active (S)- tert -butyl glycidyl ether see: Thakur, S. S.; Li, W.-J.; Shin, C.-K.; Kim, G.-J. Chirality 2005, (Volume Date 2006), 18, 37.
49. Kim, M.-J.; Lim, I. T.; Choi, G.-B.; Whang, S.-Y.; Ku, B.-C.; Choi, J.-Y. Bioorg. Med. Chem. Lett. 1996, 6, 71
50. Kotik, M.; Brichac, J.; Kyslik, P. J. Biotechnol. 2005, 120, 364
51. Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307 and references cited therein
52. The lower boiling (S)- 14 was separated from the higher-boiling (R)- tert -butyl glyceryl ether by distillation.
53. When the reaction mixture was warmed up and stirred at ambient temperature, increasing racemization was observed (1 h: 0.75%; 24 h: 23% (S)- 28 formation).
54. 3 or DIPEA (5 mol%). As solution in DCM (R)- 28 was stable at ambient temperature for two days without any additive. Although the corresponding mesylate, tosylate and nosylate derivatives were stable compounds, only the triflate (R)- 28 was sufficiently reactive to effect a selective and efficient malonate substitution.
55. In order to minimize HF elimination to the cyclopropane side product (S)- 29a, the excess of sodium dimethyl malonate (1.1 equiv) was kept as low as possible. With ≥2 equiv sodium dimethyl malonate, the intermediate (S)-29 was completely converted into (S)- 29a.
56. 4.
57. The additive DMI was superior to DMPU and preferred over the highly toxic HMPA; cf.: Al Abed, Y.; Zaman, F.; Shekhani, M. S.; Fatima, A.; Voelter, W. Tetrahedron Lett. 1992, 33, 3305
58. (R) -Glycidyl 3-nitrobenzenesulfonate (R)- 33 was offered in bulk quantity by an external supplier.
59. Pirrung, M. C.; Dunlap, S. E.; Trinks, U. P. Helv. Chim. Acta 1989, 72, 1301
60. Kitaori, K.; Mikami, M.; Furukawa, Y.; Yoshimoto, H.; Otera, J. Synlett 1998, 499
61. Mikami, M.; Furukawa, Y.; Oodera, J.; Yoshimoto, P. H. (Daiso Co., Ltd.). Jpn. Pat. JP 10059955, 1998.
62. 3N), Honeywell No. 1790. For HF addition to activated cyclopropane rings see: Cotterill, I. C.; Finch, H.; Highcock, R. M.; Holt, R. A.; Mahon, M. F.; Molloy, K. C.; Morris, J. G.; Roberts, S. M.; Short, K. M.; Sik, V. J. Chem. Soc., Perkin Trans. 1 1990, 1353
63. 3) or thermal conditions (GC, ≥200 °C) the lactones 30 and 35 partially eliminate HX providing cyclopropanolactone 34.
64. 3N • 3HF were performed in HF-resistant perfluoro-alkoxy-copolymer PFA-flasks (Supplier: Bohlender GmbH, Waltersberg 8, D-97947 Grünsfeld).
65. Cf. Steffen, K.-D. (Hüls AG). U.S. Patent 5,463,111, 1995.
66. 4 (S)- 29a is further converted into cyclopropanolactone 34 and hydroxymethyl lactone 7 which were observed as trace byproducts.