Boron tribromide → [(4'-Chloro-3-hydroxy-biphenyl-4-carbonyl)-amino]-acetic acid

HRID 1908294Notes

Reaction equation

HRID 1908294 reaction equation
C([O:3][C:4](=[O:24])[CH2:5][NH:6][C:7]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[CH:11][C:10]=1[O:22]C)=[O:8])C.B(Br)(Br)Br>C(Cl)Cl>[Cl:21][C:18]1[CH:17]=[CH:16][C:15]([C:12]2[CH:13]=[CH:14][C:9]([C:7]([NH:6][CH2:5][C:4]([OH:24])=[O:3])=[O:8])=[C:10]([OH:22])[CH:11]=2)=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 24891040[(4'-Chloro-3-methoxy-biphenyl-4-carbonyl)-amino]-acetic acid ethyl ester

Product 1

HCID 24891041[(4'-Chloro-3-hydroxy-biphenyl-4-carbonyl)-amino]-acetic acidYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of [(4′-chloro-3-methoxy-biphenyl-4-carbonyl)-amino]-acetic acid ethyl ester (0.053 g, 0.152 mmol) in CH2Cl2 (2 mL) at room temperature under nitrogen is added BBr3 (1.52 ml of a 1M solution in CH2Cl2, 1.52 mmol) dropwise. The resulting mixture is stirred for 3 days after which time the reaction is quenched with H2O (0.5 mL) then acidified to pH 1 with conc. HCl. The mixture is extracted with EtOAc (×2), the organic phase separated, dried (MgSO4), filtered and concentrated under reduced pressure. The crude material is purified by preparative HPLC to afford 0.019 g (41% yield) of the desired product as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.41 (1H, s), 9.19 (1H, s), 7.96 (1H, d, J=8.3 Hz), 7.74 (2H, d, J=8.7 Hz), 7.54 (2H, d, J=8.7 Hz), 7.21 (1H, d, J=1.7 Hz), 7.26 (1H, dd, J=8.3, 1.8 Hz), 3.99 (2H, d, J=5.5 Hz). HPLC-MS: m/z 306 [M+H]+.

Workup

  1. customis quenched with H2O (0.5 mL)
  2. extractionThe mixture is extracted with EtOAc (×2)
  3. customthe organic phase separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material is purified by preparative HPLC

Sources & evidence

ORD record
ord-a82b84bcce4b433591864779559fca7d
Source dataset
uspto-grants-2013_12
Patent number
US08598210B2

Reaction notes

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