(3-Chlorophenyl)boronic acid → (R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3'-chlorobiphenyl-4-yl)butanoate

HRID 1945058Notes

Reaction equation

HRID 1945058 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:10][C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[CH:4][CH:3]=1.[Cl:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1>C1(C)C=CC=CC=1.[Cl-].[Na+].O.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:25]([O:24][C:22]([NH:21][C@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:34]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:29])[CH:35]=2)=[CH:3][CH:4]=1)[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

7

Reactant 2

HCID 2734323(3-Chlorophenyl)boronic acidHCID 59607538(R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate

Product 1

HCID 59607651(R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3'-chlorobiphenyl-4-yl)butanoateYield 48.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
95 °C

Procedure

A suspension of give (R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (2.00 g, 4.46 mmol), 3-chlorophenylboronic acid (1.046 g, 6.69 mmol), Pd(PPh3)4 (0.515 g, 0.446 mmol) and Na2CO3aq (4.46 ml, 8.92 mmol) in Toluene (30 ml) is allowed to stir under nitrogen at 95° C. for 19 hr. The reaction mixture is cooled to ambient temperature, and diluted with brine and EtOAc. The products are extracted twice with EtOAc, washed with brine, dried over MgSO4, filtered, and concentrated. The residue is purified by flash column chromatography on 90 g silica gel (eluent: heptane/EtOAc=100:0 to 65:35) to give (R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate (1.03 g); HPLC retention time=1.74 minutes (condition B); MS (ES+)=380.2 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 9H) 2.52 (A of ABX, Jab=15.9 Hz, Jax=5.8 Hz, 1H) 2.58 (B of ABX, Jab=15.9 Hz, Jbx=5.6 Hz, 1H) 2.81-2.98 (m, 2H) 4.19 (br s, 1H) 5.07 (br d, 1H) 5.12 (A of AB, J=12.3 Hz, 1H) 5.17 (A of AB, J=12.3 Hz, 1H) 7.20-7.22 (m, 2H) 7.28-7.39 (m, 7H) 7.42-7.47 (m, 3H) 7.53-7.54 (m, 1H).

Workup

  1. temperatureThe reaction mixture is cooled to ambient temperature
  2. extractionThe products are extracted twice with EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by flash column chromatography on 90 g silica gel (eluent: heptane/EtOAc=100:0 to 65:35)

Sources & evidence

ORD record
ord-ab37471f30424ed09af6f7f215726cb7
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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