Carbon dioxide methanol → tert-Butyl (4aS,7aS)-7a-(2-fluoro-5-(5-fluoropicolinamido)phenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-ylcarbamate

HRID 2060770Notes

Reaction equation

HRID 2060770 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][N:11]=2)=[CH:4][C:3]=1[C:18]12[CH2:26][O:25][CH2:24][CH:23]1[CH2:22][S:21][C:20]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[N:19]2.CO.C(=O)=O>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][N:11]=2)=[CH:4][C:3]=1[C@:18]12[CH2:26][O:25][CH2:24][C@H:23]1[CH2:22][S:21][C:20]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[N:19]2

Participants

3

Reactant 2

HCID 21973728Carbon dioxide methanolHCID 66861447tert-butyl 7a-(5-(5-fluoropicolinamido)-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-ylcarbamate

Product 1

HCID 58102210tert-Butyl (4aS,7aS)-7a-(2-fluoro-5-(5-fluoropicolinamido)phenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-ylcarbamateYield 41%

Procedure

Racemic tert-butyl (4aSR,7aSR)-7a-(2-fluoro-5-(5-fluoropicolinamido)phenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-ylcarbamate (0.226 g, 0.460 mmol) is purified by chiral HPLC: 2.1×25 cm Chiralcel OD-H, 5 micron column, 30% methanol/CO2, flow rate: 70 mL/min, UV: 230 nm. The second eluting isomer is isolated to provide the enantiomerically enriched title compound (0.092 g, 41%). ES/MS (m/e): 491 (M+1).

Workup

  1. customThe second eluting isomer is isolated

Sources & evidence

ORD record
ord-77e3caacc4514c23ace08ee8fd960a2b
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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