Water → (2R,4R)-1-tert-butyl 2-methyl 4-(benzyloxymethoxy)pyrrolidine-1,2-dicarboxylate

HRID 869656Notes

Reaction equation

HRID 869656 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.C(N(CC)C(C)C)(C)C.Cl[CH2:28][O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.O>ClCCl>[CH2:30]([O:29][CH2:28][O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 137983Benzyl chloromethyl etherHCID 6951202(2R,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 66960641(2R,4R)-1-tert-butyl 2-methyl 4-(benzyloxymethoxy)pyrrolidine-1,2-dicarboxylateYield 72.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (2.12 g, 8.65 mmol) and N,N-diisopropylethylamine (3.01 mL, 17.3 mmol) in dichloromethane (30 mL) was added benzyl chloromethyl ether (2.71 g, 17.3 mmol). After stirring at room temperature for 18 h, the mixture was poured into water. The aqueous layer was extracted with dichloromethane three times. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to afford an oil. The residual oil was purified by silica gel column chromatography (ethyl acetate/hexane 1:4 to 1:3) to give 2.29 g (72%) of the title compound as a colorless oil.

Workup

  1. extractionThe aqueous layer was extracted with dichloromethane three times
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customto afford an oil
  5. customThe residual oil was purified by silica gel column chromatography (ethyl acetate/hexane 1:4 to 1:3)

Sources & evidence

ORD record
ord-e38c4449fc1e4454b66052f029ce9b1f
Source dataset
uspto-grants-2015_03
Patent number
US08969383B2

Reaction notes

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