Triethylamine → (RS)-N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-chloro-N-(4-methoxy-benzyl)-2-phenyl-acetamide

HRID 1929501Notes

Reaction equation

HRID 1929501 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:29])=[C:6]([C@:8]([NH:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)([CH3:18])[CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH:7]=1.C(N(CC)CC)C.[Cl:37][CH:38]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:39](Cl)=[O:40]>C(#N)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:29])=[C:6]([C@:8]([N:19]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=2)[C:39](=[O:40])[CH:38]([Cl:37])[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([CH3:18])[CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:12])[CH3:13])[CH:7]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 102902Chloro(phenyl)acetyl chloride2×HCID 66931457[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-(4-methoxy-benzyl)-amine

Product 1

HCID 58155255(RS)-N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-chloro-N-(4-methoxy-benzyl)-2-phenyl-acetamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Conditions

Temperature
10 °C

Procedure

A solution of [(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-(4-methoxy-benzyl)-amine (1.035 g, 2.15 mmol) in acetonitrile (16 ml) was treated with triethylamine (0.36 ml, 2.57 mmol). The mixture was cooled to 10° C. and a solution of (RS)-2-chloro-2-phenyl-acetyl chloride (0.34 ml, 2.36 mmol) in acetonitrile (2 ml) was added slowly. The reaction mixture was allowed to warm to room temperature and was stirred for 3 hours. Because the transformation was not complete, triethylamine (0.33 ml, 2.36 mmol) was again added, the reaction mixture cooled to −5° C., then treated with a solution of (RS)-2-chloro-2-phenyl-acetyl chloride (0.31 ml, 2.15 mmol) in acetonitrile (1 ml). The reaction mixture was allowed to warm to room temperature and was stirred for 22 hours. Thereafter, the mixture was evaporated at reduced pressure and without further workup directly purified by chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 70/30 as the eluent. (RS)-N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-chloro-N-(4-methoxy-benzyl)-2-phenyl-acetamide was obtained as a white foam (1.068 g, 78% of theory). Mass (calculated) C31H38BrClFNO3 [635.09]; (found) [M+H]+=638, [M+2-H]+=636, [M+4-H]+=634.

Workup

  1. temperatureto warm to room temperature
  2. temperaturethe reaction mixture cooled to −5° C.
  3. temperatureto warm to room temperature
  4. stirringwas stirred for 22 hours
  5. customThereafter, the mixture was evaporated at reduced pressure and without further workup
  6. customdirectly purified by chromatography on Silicycle-Si-amine column

Sources & evidence

ORD record
ord-4dd43f3a853640159216d6f09e41b370
Source dataset
uspto-grants-2012_05
Patent number
US08188079B2

Reaction notes

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