Ethyl bromoacetate → (3S,4S)-3-azido-4-ethoxycarbonylmethoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1162719Notes

Reaction equation

[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([OH:15])[C@@H:12]([N:16]=[N+:17]=[N-:18])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22]>CN(C=O)C.CCOC(C)=O>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([O:15][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[C@@H:12]([N:16]=[N+:17]=[N-:18])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

Conditions

Temperature: 0 °C

Procedure

96.1 A suspension of 210 mg NaH (55% in mineral oil) in 3 ml DMF was treated at 0° C. with 1.0 g (3S,4S)-3-azido-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester in 6 ml DMF. The reaction mixture was stirred at 0° C. for 90 min, then it was cooled to 0° C. A solution of 0.53 ml ethyl bromoacetate was added dropwise. The reaction mixture was slowly warmed to r.t., stirred overnight, then heated for 1 hr at 50° C. After cooling to r.t. the mixture was taken up in EtOAc and washed with H2O. The combined organics were dried over MgSO4, filtrated and concentrated. The crude product was purified by column chromatography (silica gel; cyclohexane->cyclohexane/EtOAc 3:2) to give 584 mg (3S,4S)-3-azido-4-ethoxycarbonylmethoxy-pyrrolidine-1-carboxylic acid tert-butyl ester as yellow liquid. MS 315.2 ([M+H]+)

Workup

temperatureit was cooled to 0° C
temperatureThe reaction mixture was slowly warmed to r.t.
stirringstirred overnight
temperatureheated for 1 hr at 50° C
temperatureAfter cooling to r.t. the mixture
washwashed with H2O
dry with materialThe combined organics were dried over MgSO4
filtrationfiltrated
concentrationconcentrated
customThe crude product was purified by column chromatography (silica gel; cyclohexane->cyclohexane/EtOAc 3:2)

Sources & evidence

ORD record: ord-f63a02b24bcc46519187c53bd988e07f
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820699B2

Reaction notes

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