p-Toluenesulfonic acid → N-[3(S)-[(N-acetyl-L-asparaginyl)amino]-2(R)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester

HRID 267099Notes

Reaction equation

HRID 267099 reaction equation
[C:1]([O:5][C:6](=[O:42])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[CH2:12][C@@H:13]([OH:41])[C@@H:14]([NH:22][C:23](=[O:40])[C@H:24]([CH2:36][C:37](=[O:39])[NH2:38])[NH:25][C:26]([O:28]CC1C=CC=CC=1)=O)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([CH3:4])([CH3:3])[CH3:2].[C:43]1(C)C=CC(S(O)(=O)=O)=CC=1.C(OC(=O)C)(=O)C.C(N(CC)CC)C>C(O)(C)C.[Pd].N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:42])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[CH2:12][C@@H:13]([OH:41])[C@@H:14]([NH:22][C:23](=[O:40])[C@H:24]([CH2:36][C:37](=[O:39])[NH2:38])[NH:25][C:26](=[O:28])[CH3:43])[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 451719Z-Asn-Phe-psi (CH(OH)CH2N)Pro-OtBu

Product 1

HCID 70045096N-[3(S)-[(N-acetyl-L-asparaginyl)amino]-2(R)-hydroxy-4-phenylbutyl]-L-proline tert.butyl esterYield 15.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 1049PyridineSolventHCID 3776IsopropanolSolvent

Procedure

0.275 g (0.473 mmol) of N-[3(S)-[[N-(benzyloxycarbonyl)-L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester was taken up in 10 ml of isopropanol and hydrogenated for 18 hours over 50 mg of 5% palladium-on-carbon in the presence of 0.18 g (0.94 mmol) of toluene-4-sulphonic acid. The catalyst was filtered off and the filtrate was evaporated. The resulting solid was dissolved in 10 ml of dichloromethane and the solution was cooled in an ice-bath. 50 mg (0.49 mmol) of acetic anhydride were added, followed by 0.10 g (0.99 mmol) of triethylamine and 0.2 ml of pyridine. The mixture was stirred at room temperature for 1 hour. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was washed with 5% sodium bicarbonate solution and with saturated sodium chloride solution and then dried over anhydrous sodium sulphate. The solvent was removed by evaporation to give 35 mg of N-[3(S)-[(N-acetyl-L-asparaginyl)amino]-2(R)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester; Rf (System E): 0.28; MS: m/e 491 [M+H]+.

Workup

  1. filtrationThe catalyst was filtered off
  2. customthe filtrate was evaporated
  3. dissolutionThe resulting solid was dissolved in 10 ml of dichloromethane
  4. temperaturethe solution was cooled in an ice-bath
  5. customThe solvent was removed by evaporation
  6. customthe residue was partitioned between ethyl acetate and water
  7. washThe organic phase was washed with 5% sodium bicarbonate solution and with saturated sodium chloride solution
  8. dry with materialdried over anhydrous sodium sulphate
  9. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-2a68b5b79163415898ee9387f6ecab9d
Source dataset
uspto-grants-1997_07
Patent number
US05652369

Reaction notes

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