Modified chelation-controlled reduction of an N -acryloyloxazolidin-2-one

Organic Process Research and Development

Volumn 14, Issue 6, 2010, Pages 1448-1452

  Connolly, Terrence J ^a   Ding, Zhixian ^a   Gong, Yumin ^a   MacEwan, Michael F ^a   Szeliga, Jan ^a   Alimardanov, Asaf ^a  

^a WYETH RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2-METHYLTETRAHYDROFURAN; ACTIVE PHARMACEUTICAL INGREDIENTS; AMINO ALCOHOLS; CONTROLLED REDUCTION; FACIAL SELECTIVITY; ISOLATED YIELD; MAGNESIUM BROMIDE; MAGNESIUM CHLORIDES; OPTICALLY ACTIVE; SCALE-UP; SIDE REACTIONS; SIGNIFICANT DETERIORATIONS; TETRA-HYDROFURAN;

BROMINE COMPOUNDS; CHELATION; CHLORINE COMPOUNDS; DRUG PRODUCTS; REACTION INTERMEDIATES; SYNTHESIS (CHEMICAL);

MAGNESIUM;

EID: 78649676896     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op100074m     Document Type: Article

References (25)

1. Alimardanov, A.; Nikitenko, A.; Connolly, T. J.; Feigelson, G.; Chan, A. W.; Ding, Z.; Ghosh, M.; Shi, X.; Ren, J.; Hansen, E.; Farr, R.; MacEwan, M.; Tadayon, S.; Springer, D.; Kreft, A. F.; Potoski, J. R. Org. Process Res. Dev. 2009, 13, 1161-1168
2. Safety screening performed in-house generated results in line with those reported previously by Merck workers for triisopropylbenzene sulfonyl azide. See: Tuma, L. D. Thermochim. Acta 1994, 243, 161-167
3. Details on the work that enabled the conversion of 3 to 4 to be performed at 40 to 50°C have been communicated recently. See: Connolly, T. J.; Hansen, E. C.; MacEwan, M. F. Org. Process Res. Dev. 2010, 14, 466-469
4. Evans, D. A.; Britton, T. C.; Ellman, J. A.; Dorow, R. L. J. Am. Chem. Soc. 1990, 112, 4011-4030
5. The process does require that dry catalyst be used since water has a significant detrimental impact on the process. Palladium on alumina can be used in cases where handling pyrophoric, dry palladium on carbon is not acceptable.
6. Prashad, M.; Liu, Y.; Kim, H.-Y.; Repic, O.; Blacklock, T. J. Tetrahedron: Asymmetry 1999, 10, 3479-3482
7. Davies has published single-crystal data for valine-derived products related to 3 that also support the anti-relationship between the carbonyl groups of the oxazolidinone and N -acyl groups. See: Bull, S. D.; Davies, S. G.; Garner, A. C.; Kruchinin, D.; Key, M.-S.; Roberts, P. M.; Savory, E. D.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2006, 294, 5-2964
8. Adam, W.; Zhang, A. Eur. J. Org. Chem. 2004, 147, 152
9. Kanai, M.; Muraoka, A.; Tanaka, T.; Sawada, M.; Ikota, N.; Tomioka, K. Tetrahedron Lett. 1995, 36, 9349-9352
10. This screening was performed using an Endeavor Catalyst Screening System from Biotage/Argonaut. Longer reaction times at lower temperatures were not evaluated.
11. A mass of 369 corresponds to loss of HBr from 6 (m / z 449).
12. 2, and THF only. After 18 h at 65°C in THF, the relative amount of 3: 7: 6 formed was 2:1:2. Performing the same stress test in 1:1 THF/IPA provided relative amounts for 3: 7: 6 of 1:2:0.
13. Details are provided in the Supporting Information. It should be noted that both 6 and 7 were hydrolyzed in the NMR sample tube when DMSO was used as the solvent. The fraction isolated by prep-LC initially contained three components; 6, 7, and a product consistent with hydrolysis of 7. After three days, the sample contained 4 components: the three components mentioned above and the product that was the result of hydrolysis of 6. We assume that the hydrolysis product originally identified was an artifact of the prep-LC conditions since the reduction is performed under anhydrous conditions.
14. This byproduct was not isolated to determine the structure since it was a secondary byproduct resulting from hydrogenation of the primary byproducts. Limiting the amount of 6 and 7 formed during the reaction would reduce the amount of 8, regardless of structure.
15. 2.
16. In process analysis of a scale-up run performed on 1 kg of 2 showed 1.6% 2, 4.8% 7, and 5.0% 6 after 4 h of reaction.
17. 2.
18. McConville, F. X. The Pilot Plant Real Book; FXM Engineering and Design: Worcester, MA, 2002.
19. For screening purposes, all reductions were performed in THF at 50°C with 50 psig hydrogen using dry palladium on carbon (10 wt % Pd) and 1.2 equiv of additive.
20. 2 and THF were mixed.
21. A total of 32 kg of 3 was prepared in six batches. Each batch of 3 required three hydrogenations of 2 that were then combined, providing isolated batch sizes of 5.0-5.5 kg of 3.
22. 2 campaign and was in stock.
23. Partial NMR spectra for starting material in the presence and absence of magnesium salts, and in-situ FTIR and heat-flow data for hydrogenations performed in the presence and absence of magnesium chloride are available as Supporting Information.
24. In-process GC analysis showed there to be 1.9% 2-methyltetrahydrofuran present at this point.
25. After 24 h, the product had a water content of 0.03% (KF method) and residual IPA of 0.11%.