Triethylamine → HCID 68722905, compound

HRID 2381030Notes

Reaction equation

HRID 2381030 reaction equation
[CH3:1][O:2][C:3](=[O:32])[C@@H:4]([NH:21][C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:8]([OH:20])[CH:7]=1.[N:33]1([C:38](Cl)=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34]1.C(N(CC)CC)C>ClCCl.CN(C1C=CN=CC=1)C>[CH2:13]([O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][C@H:4]([NH:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[C:3]([O:2][CH3:1])=[O:32])=[CH:7][C:8]=1[O:20][C:38]([N:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1)=[O:39])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 709371-Pyrrolidinecarbonyl chloride2×HCID 11316490(S)-2-Benzyloxycarbonylamino-3-(4-benzyloxy-3-hydroxy-phenyl)-propionic acid methyl ester

Product 1

HCID 68722905HCID 68722905, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
40 °C

Procedure

(S)-2-Benzyloxycarbonylamino-3-(4-benzyloxy-3-hydroxy-phenyl)-propionic acid methyl ester (434 mg) was dissolved in dichloromethane (7 ml) and a solution of 1-pyrrolidinylcarbonyl chloride (200 mg) in dichloromethane (2 ml) was added. Triethylamine (0.22 ml) was added dropwise followed by a catalytic amount of DMAP. The mixture was stirred and heated at 40° C. overnight. The reaction was monitored by HPLC/MS and further portions of 1-pyrrolidinylcarbonyl chloride (400 mg) and triethylamine (0.4 ml) were added and heating continued at 55 C for 48 hours. The reaction mixture was diluted with dichloromethane and washed with dil HCl, with aq sodium bicarbonate and with brine. Drying (MgSO4) and evaporation gave the crude product. Silca gel chromatography, eluting with mixtures of ethyl acetate-hexane gave pyrrolidine-1-carboxylic acid 2-benzyloxy-5-((S)-2-benzyloxycarbonylamino-2-methoxycarbonyl-ethyl)-phenyl ester as a colourless gum, 364 mg; Rf 0.3 (ethyl acetate-hexane 1:1); HPLC/MS retention time 7.31 min, m/z 533 (MH+).

Workup

  1. additionwere added
  2. temperatureheating
  3. washwashed with dil HCl, with aq sodium bicarbonate and with brine
  4. customDrying
  5. custom(MgSO4) and evaporation
  6. customgave the crude product
  7. washSilca gel chromatography, eluting with mixtures of ethyl acetate-hexane

Sources & evidence

ORD record
ord-ff6dba950d1a403a9f954be8d0d33449
Source dataset
uspto-grants-2012_09
Patent number
US08258097B2

Reaction notes

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