p-Toluenesulfonic acid → Phenylmethyl N-[2-[[hydroxy[2-phenyl-1-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]methyl]-1-oxo-3-phenylpropyl]-L-phenylalaninate

HRID 1058761Notes

Reaction equation

HRID 1058761 reaction equation
[OH:1][P:2]([CH:16]([NH:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([CH2:4][CH:5]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:6](O)=[O:7])=[O:3].[NH2:35][C@H:36]([C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[OH:3][P:2]([CH2:4][CH:5]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:6]([NH:35][C@H:36]([C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:7])([CH:16]([NH:24][C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:1]

Participants

7

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 736312Benzyl 3-phenyl-L-alaninateHCID 186687012-Benzyl-3-[(1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl)(hydroxy)phosphoryl]propanoic acid

Product 1

HCID 15383285Phenylmethyl N-[2-[[hydroxy[2-phenyl-1-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]methyl]-1-oxo-3-phenylpropyl]-L-phenylalaninateYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 200 mg (0.42 mmol) of 3-[hydroxy[2-phenyl-1-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]-2-(phenylmethyl)propanoic acid, 178 mg (0.42 mmol) of phenylmethyl L-phenylalaninate in the form of the p-toluenesulphonic acid salt and 384 mg (0.87 mmol) of BOP in 0.8 ml of dimethylformamide is added, with stirring at a temperature in the region of 20° C., 0.7 ml of diisopropylethylamine. After reaction for 30 minutes at this temperature, the dimethylformamide is evaporated off under reduced pressure and 12 ml of 1N hydrochloric acid are added to the oily residue obtained. The precipitate is filtered off, washed with water and dried. 210 mg of product are recovered (yield=70.3%).

Workup

  1. customAfter reaction for 30 minutes at this temperature
  2. customthe dimethylformamide is evaporated off under reduced pressure and 12 ml of 1N hydrochloric acid
  3. additionare added to the oily residue
  4. customobtained
  5. filtrationThe precipitate is filtered off
  6. washwashed with water
  7. customdried
  8. custom210 mg of product are recovered (yield=70.3%)

Sources & evidence

ORD record
ord-700a7e98156145dcad7e45b713eac1ab
Source dataset
uspto-grants-2003_02
Patent number
US06518260B1

Reaction notes

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