4-Bromobenzoic acid → (S)-4-bromo-N-(2-hydroxy-1-phenylethyl)benzamide

HRID 595788Notes

Reaction equation

HRID 595788 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[NH2:11][C@@H:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:13][OH:14].CCN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:11][C@@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][OH:14])=[O:8])=[CH:9][CH:10]=1

Participants

7

Reactant 5

HCID 114644-Bromobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1347972-Amino-2-phenylethan-1-olHCID 2733179PyBroP

Product 1

HCID 113356449(S)-4-bromo-N-(2-hydroxy-1-phenylethyl)benzamideYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-bromobenzoic acid (892 mg, 4.44 mmol) in THF (9.9 mL) was added (S)-2-amino-2-phenylethanol (609 mg, 4.44 mmol), DIEA (1.9 mL, 11.1 mmol), PyBroP (2.5 g, 5.32 mmol), and HOBT (815 mg, 5.32 mmol). The reaction mixture was stirred at room temperature for 20 h. The reaction mixture was extracted with EtOAc. The organic layer was washed with water and brine. After dried over anhydrous sodium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography (gradient EtOAc in DCM) yielding (S)-4-bromo-N-(2-hydroxy-1-phenylethyl)benzamide (850 mg, 60%). LCMS (m/z): 338.1 (MH+), 0.61 min.

Workup

  1. extractionThe reaction mixture was extracted with EtOAc
  2. washThe organic layer was washed with water and brine
  3. dry with materialAfter dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe crude product was purified by flash chromatography (gradient EtOAc in DCM)

Sources & evidence

ORD record
ord-4f88b6f070cb4ea1a42439300dbb92ce
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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