Hydrochloric Acid → Ethyl 3-[1,1'-biphenyl]-4-yl-2-[[hydroxy[2-phenyl-1-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]methyl]propanoate

HRID 1058768Notes

Reaction equation

HRID 1058768 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([CH2:15][P:16]([OH:37])([CH:18]([NH:26][C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[C:38]1(B(O)O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>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(OCC)(=O)C.C1(C)C=CC=CC=1.CO>[C:2]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([CH2:15][P:16]([OH:37])([CH:18]([NH:26][C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 18668696Ethyl 3-(4-bromophenyl)-2-[[hydroxy[2-phenyl-1-[[(phenyl-methoxy)carbonyl]amino]ethyl]phosphinyl]methyl]propanoate

Product 1

HCID 18668669Ethyl 3-[1,1'-biphenyl]-4-yl-2-[[hydroxy[2-phenyl-1-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]methyl]propanoateYield 90.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 21867641Toluene methanolSolvent

Procedure

200 mg (0.34 mmol) of ethyl 3-(4-bromophenyl)-2-[[hydroxy[2-phenyl-1-[[(phenyl-methoxy)carbonyl]amino]ethyl]phosphinyl]methyl]propanoate are condensed with 42 mg (0.34 mmol) of phenylboronic acid, working in 1.8 ml of a 2/1 toluene/methanol mixture, tetrakis(triphenylphosphine)palladium and 0.4 ml of 2M sodium carbonate (0.8 mmol). The reaction mixture is stirred for 6 hours under nitrogen and at reflux. After cooling, 10 ml of ethyl acetate are added and the mixture is acidified to pH=3 with aqueous 2N hydrochloric acid solution. After filtration through Celite, rinsed with ethyl acetate, the solvent is evaporated off under reduced pressure. The product is purified by recrystallization from a mixture of ethyl acetate and hexane. 180 mg of product are recovered (yield=90.4%).

Workup

  1. temperatureat reflux
  2. temperatureAfter cooling
  3. filtrationAfter filtration through Celite
  4. washrinsed with ethyl acetate
  5. customthe solvent is evaporated off under reduced pressure
  6. customThe product is purified by recrystallization from a mixture of ethyl acetate and hexane
  7. custom180 mg of product are recovered (yield=90.4%)

Sources & evidence

ORD record
ord-1b9c09e4ebac48ef977bbbe3afd9c49c
Source dataset
uspto-grants-2003_02
Patent number
US06518260B1

Reaction notes

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