3-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride) → 3-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic Acid Methyl Ester

HRID 2373779Notes

Reaction equation

HRID 2373779 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:18][C:19](=[O:28])[C:20]1[CH:25]=[C:24](Br)[C:23](O)=[CH:22][CH:21]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[Cl:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:36]=1[F:37].C[Si](Br)(C)C.C(O)(C(F)(F)F)=[O:47].C(Cl)Cl>>[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:18][C:19]([C:20]1[CH:21]=[C:22]([C:33]2[CH:34]=[CH:35][C:36]([F:37])=[C:31]([Cl:30])[CH:32]=2)[CH:23]=[CH:24][C:25]=1[OH:47])=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1

Participants

4

Reactant 3

HCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 692051283-(biphenyl-4-yl)-(2S)-(5-bromo-4-hydroxy-benzoylamino)-propionic acid methyl esterHCID 86597135TMSBr TFA DCM

Product 1

HCID 113865603-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic Acid Methyl Ester

Procedure

The resin-bound 3-(biphenyl-4-yl)-(2S)-(5-bromo-4-hydroxy-benzoylamino)-propionic acid methyl ester (50 mg, 0.3 mmol) was reacted with 3-chloro-4-fluorophenylboronic acid (240 mg, 1.5 mmol) following general procedure D, cleaved with TMSBr/TFA/DCM (1:1:5) at rt for 4 h. The residue obtained after removing the solvent was purified by chromatography to give 35 mg of title compound.

Workup

  1. customThe residue obtained
  2. customafter removing the solvent
  3. customwas purified by chromatography

Sources & evidence

ORD record
ord-937c882b8d5c438cb8e446fa8bc2c15f
Source dataset
uspto-grants-2008_12
Patent number
US07459472B2

Reaction notes

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