Tetrahydrofuran → Methyl N-({[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}carbonyl)serinate

HRID 1867601Notes

Reaction equation

[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.Cl.[CH3:23][O:24][C:25](=[O:30])[CH:26]([CH2:28][OH:29])[NH2:27].[O:31]1CCC[CH2:32]1>CN(C)C=O>[C:11]([O:10][C:8]([N:5]1[CH2:4][CH2:3][CH:2]([NH:1][C:32]([NH:27][C@H:26]([C:25]([O:24][CH3:23])=[O:30])[CH2:28][OH:29])=[O:31])[CH2:7][CH2:6]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: 50 °C

Procedure

4-Amino-1-boc-piperidine (600 mg, 3.0 mmol) and triethylamine (0.417 mL, 3.0 mmol) in tetrahydrofuran (16 mL) were added to a solution of p-nitrophenylchloroformate (604 mg, 3.0 mmol) at 0° C. After 1 h, additional triethylamine was added (1.25 mL, 9 mmol) along with DL-serine methyl ester hydrochloride (571 mg, 4.79 mmol) in dimethylformamide (5 mL). The reaction was heated to 50° C. for 16 h. The mixture was concentrated and redissolved in ethyl acetate. The ethyl acetate layer was washed with 1 N sodium hydroxide solution (3×), water, brine, and dried over sodium sulfate. Purification by silica gel chromatography (100% dichloromethane→8% methanol {1% ammonium hydroxide}/dichloromethane) gave the title compound (700 mg). MS 346.22 (M+1)

Workup

concentrationThe mixture was concentrated
dissolutionredissolved in ethyl acetate
washThe ethyl acetate layer was washed with 1 N sodium hydroxide solution (3×), water, brine
dry with materialdried over sodium sulfate
customPurification by silica gel chromatography (100% dichloromethane→8% methanol {1% ammonium hydroxide}/dichloromethane)

Sources & evidence

ORD record: ord-0140bb285c89413087271866040fb85d
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07632832B2

Reaction notes

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