Benzyl Alcohol → tert-Butyl 4-{[(benzyloxy)carbonyl]amino}-4-methylpiperidine-1-carboxylate

HRID 1642672Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH3:17])(C(O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:20]([CH2:23]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:32])C=CC=CC=1.[CH2:42]([OH:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([NH:20][C:23]([O:49][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:32])([CH3:17])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of the 4-methyl-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (5 g, 20.6 mmol) in toluene (40 mL) at 23° C. was added triethylamine (4.3 mL, 31 mmol) and diphenylphosphoryl azide (6.1 mL, 28.0 mmol). The resulting mixture was stirred at 23° C. for 45 minutes after which benzyl alcohol (11.1 mL, 103 mmol) was added. The reaction mixture was then heated to 80° C. for 16 hours. The reaction mixture was allowed to cool to room temperature and the excess solvents were removed under reduced pressure. The crude residue was purified by chromatography (silica gel, eluting with 10% ethyl acetate/90% hexane to 30% ethyl acetate/70% hexane) to provide the titled compound (5.6 grams). MS (CI) m/z 249 (M−99)+; 1H NMR (300 MHz, CDCl3) δ ppm 7.38-7.31 (m, 5H), 5.05 (s, 2H), 4.57 (s, 1H), 3.67-3.60 (m, 2H), 3.18 (m, 2H), 1.98-1.90 (m, 2H), 1.44 (s, 9H), 1.37 (s, 3H).

Workup

additionwas added
temperatureto cool to room temperature
customthe excess solvents were removed under reduced pressure
customThe crude residue was purified by chromatography (silica gel, eluting with 10% ethyl acetate/90% hexane to 30% ethyl acetate/70% hexane)

Sources & evidence

ORD record: ord-10179ea3ac334a9bbb598cbd7149fec8
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119664B2

Reaction notes

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