A one-pot and efficient preparation of (S)-benzyl 4-hydroxy-2-pentynoate from (S)-3-butyn-2-ol using an unusual lithiation with n-BuLi and a catalytic amount of hexamethyldisilazane

Synthetic Communications

Volumn 29, Issue 17, 1999, Pages 3011-3016

  Lai, Gaifa ^a,b   Colon, Cesar ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZYL 4 HYDROXY 2 PENTYNOATE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; CATALYSIS; DRUG SYNTHESIS; DRUG USE;

EID: 0032808157     PISSN: 00397911     EISSN: None     Source Type: Journal    
DOI: 10.1080/00397919908086476     Document Type: Article

References (12)

1. For an excellent recent example of one-pot transformations, see: Misner, J. W.; Kennedy, J. H.; Biggs, W. S. Org. Proc. Res. Develop. 1997, 1, 77.
2. (a) Malaska, M, J.; Fauq, A. H.; Kozikowski, A. P.; Aagaard, P. J.; McKinney, M. Bioorg. Med. Chem. Lett. 1995, 5, 61.
3. (b) Chackalamannil, S.; Davies, R, J.; Asberom, T.; Doller, D.; Leone, D. J. Am. Chem. Soc. 1996, 118, 9812.
4. (S)-3-Butyn-2-ol (2) was purchased from Aldrich Chemical Company.
5. (S)-3-Butyn-2-ol (2) was also resolved from its racemic mixture via reaction with phthalic anhydride in tert-butyl methyl ether, followed by treatment with (R)-1-phenylethylamine.
6. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Chemistry, 2nd ed.; J. Wiley and Sons, Inc.: New York, 1991.
7. 3) for the silyl ether 5: δ 4.28-4.23 (dq, J = 2.0, 6.5 Hz, 1 H), 2.23 (d, J = 2.1 Hz, 1 H), 1.16 (d, J = 6.6 Hz, 3 H), -0.08 (s, 9 H).
8. We observed that the silylation was very slow when the mixture of solvent and alcohol 2 appeared neutral or slightly basic (pH 7-8).
9. 3) δ 7.40-7.30 (m, 5 H), 5.15 (s, 2 H), 4.05 (low but very broad, 2 H), 1.23 (d, J = 6.8 Hz, 12 H).
10. Murray, W.; Wachter, M.; Barton, D.; Forero-Kelly, Y. Synthesis 1991, 18.
11. 2O. The disappearance of the doublet peak near 2.23 ppm on the spectrum indicated the complete lithiation of the silyl ether 5.
12. 2O (40:60); flow rate, 1.0 mL/min; detector, 230 nm; room temperature.