Benzyl chloroformate → (3R,4R)-rel-tert-Butyl 4-(((benzyloxy)carbonyl)amino)-3-hydroxypiperidine-1-carboxylate

HRID 1972091Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH2:14])[C@H:10]([OH:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Cl[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[C@H:10]([OH:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 2.5 °C

Procedure

To a stirred solution of (±)-trans-4-amino-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (9.48 mmol, 2.05 g) in a biphasic mixture of DCM (10 mL) and saturated sodium bicarbonate (10 mL) at 0° C. was added benzyl chloroformate (2.0 mL) drop-wise and continued stirring at 0-5° C. for 1 h. The organic layer was separated, and the aqueous layer was extracted with DCM. The combined organic layers were dried, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography by eluting with 50% ethyl acetate in hexanes to provide (±)-trans-4-benzyloxycarbonylamino-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester.

Workup

customThe organic layer was separated
extractionthe aqueous layer was extracted with DCM
customThe combined organic layers were dried
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by flash silica gel column chromatography
washby eluting with 50% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-4b31da2b7de24f7cba468f3e38e95fb4
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431575B2

Reaction notes

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