(R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-one → HCID 86693410, compound

HRID 575367Notes

Reaction equation

HRID 575367 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:15][CH2:14][CH:13]([F:16])[C:12]3[S:11][C:10]([C:17]([O:19][CH3:20])=[O:18])=[N:9][C:8]=3[C:6]=2[CH:7]=1.[C:21]([C@:23]1([OH:30])[CH2:27][CH2:26][N:25]([CH3:28])[C:24]1=[O:29])#[CH:22]>>[F:16][CH:13]1[C:12]2[S:11][C:10]([C:17]([O:19][CH3:20])=[O:18])=[N:9][C:8]=2[C:6]2[CH:7]=[C:2]([C:22]#[C:21][C@:23]3([OH:30])[CH2:27][CH2:26][N:25]([CH3:28])[C:24]3=[O:29])[CH:3]=[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 86693411HCID 86693411, compound

Product 1

HCID 86693410HCID 86693410, compound

Procedure

Methyl 9-bromo-4-hydroxy-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxylate was reacted similarly to as described in General Procedure P with non-critical modifications to afford 142 mg (94%) of methyl 9-bromo-4-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxylate. Methyl 9-bromo-4-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxylate 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 methyl 4-fluoro-9-[2-[(3R)-3-hydroxy-1-methyl-2-oxo-pyrrolidin-3-yl]ethynyl]-4,5-dihydro-[1]benzoxepin o[5,4-d]thiazole-2-carboxylate which was directed subjected to General Procedure M to afford 29 mg and 30 mg (37% 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-24a1b01f6237418dbc2b3d83fac59701
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…