Piperidine → (R)-tert-butyl 3-(piperidin-1-yl)pyrrolidine-1-carboxylate

HRID 2040953Notes

Reaction equation

CS(O[C@H:6]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7]1)(=O)=O.[NH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>>[N:18]1([C@@H:6]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7]2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

Reactant 2

HCID 8082Piperidine

HCID 11032777(S)-1-Boc-3-methanesulfonyloxy-pyrrolidine

Product 1

HCID 66905725(R)-tert-butyl 3-(piperidin-1-yl)pyrrolidine-1-carboxylate

Conditions

Temperature: 70 °C

Procedure

A mixture of (S)-tert-butyl 3-(methylsulfonyloxy)pyrrolidine-1-carboxylate (Reference Example 5a, 12.15 g, 45.8 mmol) and piperidine (100 mL, 1.01568 mole) was stirred at 70° C. overnight. The residue was purified by silica gel chromatography (100% ethyl acetate to 97:3 ethyl acetate/methanol). Fractions containing product were combined and concentrated under reduced pressure to give (R)-tert-butyl 3-(piperidin-1-yl)pyrrolidine-1-carboxylate. 1H NMR (300 MHz, CD3OD) δ ppm 1.45 (s, 9H), 1.45-1.53 (m, 2H), 1.56-1.66 (m, 1H), 1.66-1.84 (m, 1H), 2.09-2.20 (m, 1H), 2.35-2.60 (m, 4H), 2.73-2.89 (m, 1H), 3.06 (t, J=10 Hz, 1H), 3.17-3.29 (m, 1H), 3.51 (t, J=10 Hz, 1H), 3.58-3.66 (m, 1H); MS (DCI/NH3) m/z 255 (M+H)+.

Workup

customThe residue was purified by silica gel chromatography (100% ethyl acetate to 97:3 ethyl acetate/methanol)
additionFractions containing product
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-4fdf7c18c3424a91a44a440f79242784
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580968B2

Reaction notes

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