Benzyl chloroformate → Benzyl 4-oxopiperidine-1-carboxylate

HRID 2388684Notes

Reaction equation

Cl.[NH:2]1[CH2:7][CH2:6][C:5](=[O:8])[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].[C:15](Cl)([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].C(OCC)(=O)C.CCCCCC>O1CCCC1.O>[O:8]=[C:5]1[CH2:6][CH2:7][N:2]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:3][CH2:4]1

Participants

Conditions

Temperature: 2.5 °C

Procedure

To a solution of piperidin-4-one hydrochloride (32 g, 0.23 mol) in tetrahydrofuran (320 ml, 10×) was added K2CO3 (64.2 g) dissolved in water (160 ml) at room temperature. The mixture was cooled to 0-5° C. and then Cbz chloride (50%) (74.28 ml, 1.1 eq.) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 1-2 h. Progress of the reaction was monitored by TLC (30% ethyl acetate/hexane). Upon disappearance of the starting material the mixture was filtered and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×300 ml) and the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica, 12% ethyl acetate/hexane). Yield: 40.7 g (74%)

Workup

temperatureThe reaction mixture was warmed to room temperature
filtrationUpon disappearance of the starting material the mixture was filtered
customthe layers were separated
extractionThe aqueous layer was extracted with ethyl acetate (2×300 ml)
dry with materialthe combined organic layers were dried over sodium sulfate
concentrationconcentrated under reduced pressure
customThe crude product was purified by column chromatography (silica, 12% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-5f29d4eca7c8479da55a8dccb504b6c6
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08268814B2

Reaction notes

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