Potassium Carbonate → 3-{2-(Benzoylaminomethyl)-4-[3-(biphenyl-4-yloxy)propoxy]phenyl}propionic acid tert-butyl ester

HRID 1181143Notes

Reaction equation

HRID 1181143 reaction equation
Br[CH2:2][CH2:3][CH2:4][O: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.[C:18]([O:22][C:23](=[O:43])[CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][C:27]=1[CH2:33][NH:34][C:35](=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([CH3:21])([CH3:20])[CH3:19].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[C:18]([O:22][C:23](=[O:43])[CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:8][CH:7]=2)=[CH:28][C:27]=1[CH2:33][NH:34][C:35](=[O:42])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 152334631,1'-Biphenyl, 4-(3-bromopropoxy)-HCID 589795203-[2-(Benzoylamino-methyl)4-hydroxy-phenyl]propionic acid tert-butyl ester

Product 1

HCID 692320193-{2-(Benzoylaminomethyl)-4-[3-(biphenyl-4-yloxy)propoxy]phenyl}propionic acid tert-butyl esterYield 88.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 4-(3-bromo-propoxy)-biphenyl (291 mg, 1.00 mmol; Preparation 12) and 3-[2-(benzoylamino-methyl)-4-hydroxy-phenyl]-propionic acid tert-butyl ester (320 mg, 0.90 mmol; Preparation 21) in DMF (5 mL) was treated with K2CO3 (100 mg) and heated at 60° C. for 48 h. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (3×20 mL). The combined organics were dried (Na2SO4), concentrated, and purified using silica gel chromatography (10-30% EtOAc/hexanes) to give 3-{2-(benzoylaminomethyl)-4-[3-(biphenyl-4-yloxy)propoxy]phenyl}propionic acid tert-butyl ester (450 mg). This material was treated with a mixture of CH2Cl2 (1.0 mL)/TFA (0.8 mL)/water (0.1 mL) at ambient temperature for 2 h. The reaction mixture was concentrated and dried under vacuum to afford the title product as a white solid (380 mg, 75%). MS (ES) m/e 510.1 (M+1).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organics were dried (Na2SO4)
  3. concentrationconcentrated
  4. custompurified

Sources & evidence

ORD record
ord-928482148a9644d0b52362716aa42f38
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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