(3-Chlorophenyl)boronic acid → (S)-2-(Tert-butoxycarbonylamino)-3-(3'-chlorobiphenyl-4-yl)propanoic acid

HRID 388870Notes

Reaction equation

HRID 388870 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1)=[O:7])([CH3:4])[CH3:3].[Cl:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1>COCCOC.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:2]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:26]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:21])[CH:27]=2)=[CH:13][CH:12]=1)[C:18]([OH:20])=[O:19])=[O:7])([CH3:4])([CH3:3])[CH3:1]

Participants

6

Reactant 2

HCID 2734323(3-Chlorophenyl)boronic acidHCID 2734477(2S)-3-(4-bromophenyl)-2-{[(tert-butoxy)carbonyl]amino}propanoic acid

Product 1

HCID 58280562(S)-2-(Tert-butoxycarbonylamino)-3-(3'-chlorobiphenyl-4-yl)propanoic acidYield 83%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of Boc-L-4-bromophenylalanine (15.0 g, 43.6 mmol), 3-chlorophenylboronic acid (8.52 g, 54.5 mmol), and tetrakis(triphenylphosphine)palladium(0) (1.51 g, 1.31 mmol) in 1,2-dimethoxyethane (180 mL) was added 2M solution of aqueous NaCO3 (33 mL). The reaction mixture was heated to 85° C. After stirred for 2 hours, the reaction mixture was cooled to room temperature and diluted with EtOAc. The mixture was washed with 1M HCl and brine. The organic layer was dried over Na2SO4, concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: 10% MeOH in dichloromethane) to give (S)-2-tert-butoxycarbonylamino-3-(3′-chloro-biphenyl-4-yl)-propionic acid (13.6 g). 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 3.08-3.17 (m, 1H), 3.21-3.31 (m, 1H), 4.65 (bs, 1H), 5.01 (bs, 1H), 7.23-7.32 (m, 3H), 7.45-7.50 (m, 2H), 7.52-7.60 (m, 1H), 7.63-7.70 (m, 2H); MS: m/z (MH+) 376.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. washThe mixture was washed with 1M HCl and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. custompurified by silica gel column chromatography (eluent: 10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-3d6e2b3921304f7eb20c56491ba7e07b
Source dataset
uspto-grants-2013_02
Patent number
US08377978B2

Reaction notes

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