Methylamine → (S)-tert-butyl 1-cyclohexyl-3-(methylamino)propan-2-ylcarbamate

HRID 1254204Notes

Reaction equation

CS(O[CH2:6][C@@H:7]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)(=O)=O.[CH3:23][NH2:24]>C(O)C>[CH:9]1([CH2:8][C@H:7]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:6][NH:24][CH3:23])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

Conditions

Temperature: 55 °C

Procedure

(S)-2-(tert-butoxycarbonylamino)-3-cyclohexylpropyl methanesulfonate (28 g, 83.6 mmol) was dissolved into a solution of methylamine in ethanol (about 30% by weight, 300 mL). The reaction was heated at 50-60° C. overnight and concentrated in vacuo. The residue was dissolved in EtOAc, washed with brine (2×100 mL), dried over MgSO4, and concentrated to give the crude product. This crude product was purified by flash chromatography (AcOEt:Hex.=2:1 first, then EtOAc: MeOH=1:1) to afford pure (S)-tert-butyl 1-cyclohexyl-3-(methylamino)propan-2-ylcarbamate (10.6 g, 47%). 1H NMR (400 MHz, CDCl3): 4.81 (brs, 1H), 3.89 (m, 1H), 2.77 (m, 2H), 2.54 (s, 3H), 2.44 (m, 2H), 1.78 (m, 1H), 1.67 (m, 4H), 1.44 (s, 9H), 1.50-1.10 (m, 6H), 1.00-0.77 (m, 2H), 0.05 (s, 9H). MS (E/Z): 271 (M+H+).

Workup

concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in EtOAc
washwashed with brine (2×100 mL)
dry with materialdried over MgSO4
concentrationconcentrated
customto give the crude product
customThis crude product was purified by flash chromatography (AcOEt

Sources & evidence

ORD record: ord-1ebd700f6c9849cb85309261ae163c8d
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455521B2

Reaction notes

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