Butylate → N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-acrylamide

HRID 1929496Notes

Reaction equation

HRID 1929496 reaction equation
Br[CH:2]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:3]([NH:5][C:6]([C:10]1[CH:15]=[C:14]([Br:16])[CH:13]=[CH:12][C:11]=1[F:17])([CH3:9])[CH2:7][OH:8])=[O:4].[K].CCSC(N(CC(C)C)CC(C)C)=O.C([C@H]1OC[C@@](C2C=C(Br)C=CC=2F)(C)NC1=O)C1C=CC=CC=1.C([C@@H]1OC[C@](C2C=C(Br)C=CC=2F)(C)NC1=O)C1C=CC=CC=1>>[Br:16][C:14]1[CH:13]=[CH:12][C:11]([F:17])=[C:10]([C:6]([NH:5][C:3](=[O:4])[CH:2]=[CH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)([CH3:9])[CH2:7][OH:8])[CH:15]=1

Participants

6

Reactant 5

HCID 16181ButylateHCID 5462222PotassiumHCID 58155180(2R,5S)-2-benzyl-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholin-3-oneHCID 58155233(2RS)-bromo-N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-propionamideHCID 66931472(2S,5R)-2-benzyl-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholin-3-one

Product 1

HCID 66931645N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-acrylamideYield 30%

Procedure

In analogy to the cyclization reaction described for the preparation of Building block C, the reaction of (2RS)-bromo-N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-propionamide with potassium tent-butylate yielded besides the N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-acrylamide (0.381 g, 30% of theory), (2R,5S)-2-benzyl-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholin-3-one and (2S,5R)-2-benzyl-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholin-3-one as the dominant diastereoisomer in form of a white foam (51% of theory). Mass (calculated) C18H17BrFNO2[378.244]; (found) [M+H]+=378, [M+2-H]+=380.

Workup

  1. customIn analogy to the cyclization reaction
  2. customdescribed for the preparation of Building block C

Sources & evidence

ORD record
ord-05bc10baf847443cb256355984bcc8cf
Source dataset
uspto-grants-2012_05
Patent number
US08188079B2

Reaction notes

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