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

HRID 1929495Notes

Reaction equation

HRID 1929495 reaction equation
[NH2:1][C:2]([C:6]1[CH:11]=[C:10]([Br:12])[CH:9]=[CH:8][C:7]=1[F:13])([CH3:5])[CH2:3][OH:4].C(N(CC)CC)C.Br[CH:22]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:23](Cl)=[O:24]>C(#N)C>[Br:12][C:10]1[CH:9]=[CH:8][C:7]([F:13])=[C:6]([C:2]([NH:1][C:23](=[O:24])[CH:22]=[CH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([CH3:5])[CH2:3][OH:4])[CH:11]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2630312-Bromo-3-phenylpropanoyl chlorideHCID 575142112-Amino-2-(5-bromo-2-fluorophenyl)propan-1-ol

Product 1

HCID 66931645N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-acrylamideYield 10.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of (RS)-2-amino-2-(5-bromo-2-fluoro-phenyl)-propan-1-ol (1.5 g, 6 mmol) and triethylamine (1.01 ml, 7.3 mmol) in acetonitrile (31 ml) was cooled to 0° C. A solution of (RS)-2-bromo-3-phenyl-propionyl chloride (CAS 42762-86-7) (1.637 g, 6.6 mmol) in acetonitrile was added dropwise. After complete addition the reaction mixture was left to warm to room temperature. After 1 hour the reaction mixture was evaporated under reduced pressure and directly purified by chromatography on silica gel using a gradient of heptane and ethyl acetate=100/0 to 50/50 as the eluent. Besides the N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-acrylamide (0.233 g, 10% of theory), the (2RS)-bromo-N-[(RS)-1-(5-bromo-2-fluoro-phenyl)-2-hydroxy-1-methyl-ethyl]-3-phenyl-propionamide (mixture of diastereoisomers 3:2) was obtained as a white solid (1.985 g, 71.5% of theory). Mass (calculated) C18H18Br2FNO2 [459.156]; (found) [M+H]+=457, [M+2-H]+=459, [M+4-H]+=461.

Workup

  1. additionAfter complete addition the reaction mixture
  2. waitwas left
  3. customAfter 1 hour the reaction mixture was evaporated under reduced pressure
  4. customdirectly purified by chromatography on silica gel using a gradient of heptane and ethyl acetate=100/0 to 50/50 as the eluent

Sources & evidence

ORD record
ord-5bd1cb68510740af85f1a1eb3ed4a094
Source dataset
uspto-grants-2012_05
Patent number
US08188079B2

Reaction notes

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