Boron tribromide → (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid ethyl ester

HRID 2384035Notes

Reaction equation

HRID 2384035 reaction equation
[CH2:1]([O:3][C:4](=[O:35])[C@H:5]([CH3:34])[CH2:6][C@H:7]([NH:21][C:22](=[O:33])[C:23]1[CH:28]=[C:27]([F:29])[C:26]([O:30]C)=[C:25]([F:32])[CH:24]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2].B(Br)(Br)Br>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:35])[C@H:5]([CH3:34])[CH2:6][C@H:7]([NH:21][C:22](=[O:33])[C:23]1[CH:24]=[C:25]([F:32])[C:26]([OH:30])=[C:27]([F:29])[CH:28]=1)[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13][CH:14]=1)[CH3:2]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 59608113(2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-methoxy-benzoylamino)-2-methyl-pentanoic acid ethyl ester

Product 1

HCID 67506121(2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid ethyl esterYield 82.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Next, to a solution of (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-methoxy-benzoylamino)-2-methyl-pentanoic acid ethyl ester (125 mg, 0.260 mmol) in DCM (2.6 mL) is slowly added BBr3 (2.60 mL, 2.60 mmol) under nitrogen. The reaction is stirred for 18 hours at rt. The reaction is quenched with MeOH, diluted with EtOAc, washed with H2O and brine, dried over MgSO4, and concentrated under reduced pressure. The obtained material is purified by preparative silica gel thin-layer chromatography (7% MeOH in DCM) to give 100 mg (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid ethyl ester.

Workup

  1. customThe reaction is quenched with MeOH
  2. additiondiluted with EtOAc
  3. washwashed with H2O and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained material is purified by preparative silica gel thin-layer chromatography (7% MeOH in DCM)

Sources & evidence

ORD record
ord-7ecb528f8e624aa6b269f3c36b29b690
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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