Dicyclohexylcarbodiimide → (S,R)-1-(2-tert-butoxycarbonylamino-2-phenylacetyl)-pyrrolidine-2-carboxylic acid benzyl ester

HRID 1647148Notes

Reaction equation

HRID 1647148 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@@H:9]([C:16]([OH:18])=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])([CH3:4])[CH3:3].Cl.[CH2:20]([O:27][C:28](=[O:34])[C@@H:29]1[CH2:33][CH2:32][CH2:31][NH:30]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)C(C)C)(C)C.O.ON1C2C=CC=CC=2N=N1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[NH:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@@H:9]([C:16]([N:30]1[CH2:31][CH2:32][CH2:33][C@H:29]1[C:28]([O:27][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:34])=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 2733413Proline benzyl ester hydrochlorideHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 15288611(S,R)-1-(2-tert-butoxycarbonylamino-2-phenylacetyl)-pyrrolidine-2-carboxylic acid benzyl esterYield 94.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of Boc-D-phenylglycine (15.0 g, 59.7 mmole) and proline benzyl ester hydrochloride (14.43 g, 59.7 mmole) in 60 ml of DMF was cooled to 0° C. and N,N-diisopropylethylamine (10.3 ml, 59.7 mmole) was added followed by 1-hydroxybenzotriazole hydrate (8.1 g, 59.7 mmole) and DCC (12.3 g, 59.7 mmole). The reaction mixture was stirred for 3 days at room temperature after which it was filtered and the filtrate was evaporated to an oil under vacuum. The oil was dissolved in 200 ml of ethyl acetate and 150 ml of water and after shaking the organic layer was separated, washed three times with 100 ml portions of 0.1N HCl, once with 150 ml of water, three times with 100 ml portion of 5% sodium bicarbonate and again with 150 ml of water. The washed organic solution was dried over MgSO4 and then was evaporated under vacuum to provide 24.8 g of Boc-D-Phg-Pro-OBzl as a solid (95% of theory): TLC Rf (A) 0.75; FAB-MS 439 (M+).

Workup

  1. filtrationwas filtered
  2. customthe filtrate was evaporated to an oil under vacuum
  3. dissolutionThe oil was dissolved in 200 ml of ethyl acetate
  4. stirring150 ml of water and after shaking the organic layer
  5. customwas separated
  6. washwashed three times with 100 ml portions of 0.1N HCl
  7. dry with materialThe washed organic solution was dried over MgSO4
  8. customwas evaporated under vacuum

Sources & evidence

ORD record
ord-a5f5c91f530048798f3b6ebce922bc2a
Source dataset
uspto-grants-1995_07
Patent number
US05430023

Reaction notes

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