(R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-one → HCID 86693417, compound

HRID 575371Notes

Reaction equation

HRID 575371 reaction equation
Br[C:2]1[C:3]([F:23])=[CH:4][C:5]2[O:15][CH2:14][C:13]([F:17])([CH3:16])[C:12]3[S:11][C:10]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N:9][C:8]=3[C:6]=2[CH:7]=1.[C:24]([C@:26]1([OH:33])[CH2:30][CH2:29][N:28]([CH3:31])[C:27]1=[O:32])#[CH:25]>>[F:17][C:13]1([CH3:16])[C:12]2[S:11][C:10]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N:9][C:8]=2[C:6]2[CH:7]=[C:2]([C:25]#[C:24][C@:26]3([OH:33])[CH2:30][CH2:29][N:28]([CH3:31])[C:27]3=[O:32])[C:3]([F:23])=[CH:4][C:5]=2[O:15][CH2:14]1

Participants

3

Reactant 2

HCID 86693296(R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-oneHCID 86693418HCID 86693418, compound

Product 1

HCID 86693417HCID 86693417, compound

Procedure

Ethyl 9-bromo-8-fluoro-4-hydroxy-4-methyl-5H-[1]benzoxepino[5,4-d]thiazole-2-carboxylate (170 mg) was reacted similarly to as described in General Procedure P with non-critical modifications to afford 130 mg (76%) of ethyl 9-bromo-4,8-difluoro-4-methyl-5H-[1]benzoxepino[5,4-d]thiazole-2-carboxylate. Ethyl 9-bromo-4,8-difluoro-4-methyl-5H-[1]benzoxepino[5,4-d]thiazole-2-carboxylate (122 mg) was reacted with (3R)-3-ethynyl-3-hydroxy-1-methyl-pyrrolidin-2-one similarly to as described in General Procedure F with non-critical modifications to afford ethyl 4,8-difluoro-9-[2-[(3R)-3-hydroxy-1-methyl-2-oxo-pyrrolidin-3-yl]ethynyl]-4-methyl-5H-[1]benzoxepino[5,4-d]thiazole-2-carboxylate which was directed subjected to General Procedure M to afford 7.2 mg and 6.9 mg (11% overall yield) after reverse phase purification then chiral separation. The absolute stereochemistry at the 4-fluorine substitution position for each isomer was not determined.

Sources & evidence

ORD record
ord-42286fb994c3421f92af16ba6449af2a
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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