1-Propanol → Tert-butyl 3-(benzyloxycarbonylamino)-4-hydroxy-pyrrolidine-1-carboxylate

HRID 503711

Reaction equation

[CH2:1](NC(=O)[O-])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClN1C(C)(C)[C:17](=[O:18])[N:16](Cl)C1=O.[C:23]([O:27][C:28]([N:30]1[CH2:34]C=CC1)=[O:29])([CH3:26])([CH3:25])[CH3:24].S([O-])([O-])=[O:36].[Na+].[Na+].[CH2:41]([OH:44])[CH2:42][CH3:43]>O.[OH-].[Na+].CCOC(C)=O>[C:23]([O:27][C:28]([N:30]1[CH2:34][CH:41]([OH:44])[CH:42]([NH:16][C:17]([O:18][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:36])[CH2:43]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

Conditions

Temperature: 0 °C

Procedure

N-Propanol (20 ml), benzylcarbamate (4 g, 27 mmol), and 1,3-dichloro-5,5-dimethylhydantoin (2.6 g, 13 mmol) are added to a solution of NaOH (1 g, 27 mmol) in water (40 ml). The reaction mixture is cooled to 0° C. and a solution of 2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester (1.51 g, 8.92 mmol) in n-propanol (10 ml) is added. A solution of potassium osmate (0.098 g, 0.268 mmol) in 0.65 M NaOH (1 ml) is added. The reaction mixture is stirred at 0° C. for 1 hour and then at room temperature for 2 hours. The reaction mixture is quenched with sodium sulfite (1.90 g, 15 mmol) and diluted with approximately 1:1 EtOAc:water (100 ml). The aqueous layer is extracted with ethyl acetate, the combined organic extracts dried (MgSO4) and concentrated. Purification on a silica gel column (4:1 hexanes:EtOAc) yields 3-benzyloxycarbonylamino-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

waitat room temperature for 2 hours
extractionThe aqueous layer is extracted with ethyl acetate
dry with materialthe combined organic extracts dried (MgSO4)
concentrationconcentrated
customPurification on a silica gel column (4:1 hexanes:EtOAc)

Sources & evidence

ORD record: ord-ddaaf293efb845c285160f35a6a0829f
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07777032B2

Linked notes

Loading…