Dicyclohexylcarbodiimide → (S)-Phenylmethyl 2-[[1-[[[2-(1,1-dimethylethoxy)-2-oxoethyl]amino]carbonyl]-3-methylbutoxy]methyl]-1-pyrrolidinecarboxylate

HRID 1982641Notes

Reaction equation

HRID 1982641 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C@H:12]2[CH2:16][O:17][CH:18]([C:23]([OH:25])=O)[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:26][C@H:27]([C:32]([O-:34])=[O:33])C(C)(C)C.ON1C2C=C[CH:43]=[CH:44][C:39]=2N=N1.[CH:45]1(N=C=NC2CCCCC2)CCCCC1>ClCCl.CO>[CH3:45][C:44]([CH3:43])([O:34][C:32](=[O:33])[CH2:27][NH:26][C:23]([CH:18]([O:17][CH2:16][C@@H:12]1[CH2:13][CH2:14][CH2:15][N:11]1[C:9]([O:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:10])[CH2:19][CH:20]([CH3:21])[CH3:22])=[O:25])[CH3:39]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 57212195(2S)-phenylmethyl 2-[(1-carboxy-3-methylbutoxy)methyl]-1-pyrrolidinecarboxylateHCID 77068310tert-Butylglycinate

Product 1

HCID 70468867(S)-Phenylmethyl 2-[[1-[[[2-(1,1-dimethylethoxy)-2-oxoethyl]amino]carbonyl]-3-methylbutoxy]methyl]-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(2S)-Phenylmethyl-2-[(1-carboxy-3-methylbutoxy)methyl]-1-pyrrolidinecarboxylate (center on side chain is R,S mixture), 2 g (0.0057 mol), is dissolved in 100 ml of dichloromethane, cooled to 0° C. and 1.1 g (0.0084 mol) of t-butylglycinate, 0.88 g (0.0057 mol) of 1-hydroxybenzotriazole and 1.32 g (0.0064 mol) of dicyclohexylcarbodiimide are added. The mixture is allowed to reach room temperature and stirred 14 hours, filtered, the solvent evaporated in vacuo and the residue dissolved in 200 ml of dichloromethane and washed successively with a 5% aqueous solution of sodium chloride, 2×200 ml. The dichloromethane layer is separated, dried over sodium sulfate, evaporated in vacuo and the residue purified by chromatography using silica gel and eluting with dichloromethane-methanol (98:2) to give (S)-phenylmethyl 2-[[1-[[[2-(1,1-dimethylethoxy)-2-oxoethyl]amino]carbonyl]-3-methoxy-butoxy]methyl]-1-pyrrolidinecarboxylate (2-position of pentane chain is R S), 1.75 g; [ α]D25 -70.2° (c 0.39, methanol).

Workup

  1. customto reach room temperature
  2. filtrationfiltered
  3. customthe solvent evaporated in vacuo
  4. dissolutionthe residue dissolved in 200 ml of dichloromethane
  5. washwashed successively with a 5% aqueous solution of sodium chloride, 2×200 ml
  6. customThe dichloromethane layer is separated
  7. dry with materialdried over sodium sulfate
  8. customevaporated in vacuo
  9. customthe residue purified by chromatography
  10. washeluting with dichloromethane-methanol (98:2)
  11. customto give (S)-phenylmethyl 2-[[1-[[[2-(1,1-dimethylethoxy)-2-oxoethyl]amino]carbonyl]-3-methoxy-butoxy]methyl]-1-pyrrolidinecarboxylate (2-position of pentane chain is R S), 1.75 g

Sources & evidence

ORD record
ord-4f3a0b13dad54182bff78691e37f34ac
Source dataset
uspto-grants-1986_06
Patent number
US04596819

Reaction notes

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