Triethylamine → 4-Nitrooxy-piperidine-1-carboxylic acid 4-nitro-phenyl ester
Reaction equation
Cl.[N+:2]([O-:11])([O:4][CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)=[O:3].CCN(CC)CC.Cl[C:20]([O:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)=[O:21]>C1COCC1.CC#N>[N+:29]([C:26]1[CH:25]=[CH:24][C:23]([O:22][C:20]([N:8]2[CH2:9][CH2:10][CH:5]([O:4][N+:2]([O-:11])=[O:3])[CH2:6][CH2:7]2)=[O:21])=[CH:28][CH:27]=1)([O-:31])=[O:30]Participants
5
Procedure
To a solution of Piperidin-4-yl nitrate hydrochloride (INTERMEDIATE 13, Step B) (0.40 g, 2.20 mmol) and Et3N (0.67 g, 6.60 mmol) in THF/CH3CN 2/1 (24 mL) was added 4-Nitrophenyl chloroformate (0.44 g, 2.20 mmol) as solid. After stirring at rt over night, the mixture was concentrated. The residue was diluted with EtOAc and washed with NaH2PO4 5%. The organic layer was dried over MgSO4 and concentrated. The residue was purified by flash chromatography (Biotage SP1; column SNAP 50; TLC method: n-hexane/ethyl acetate 7/3; Rf=0.37), affording the title product as a white solid. 1H-NMR (300 MHz, CDCl3); δ 8.36-8.25 (2H, m), 7.39-7.28 (2H, m), 5.30-5.18 (1H, m), 4.00-3.50 (4H, m), 2.20-2.06 (2H, m), 2.02-1.86 (2H, m).
Workup
- concentrationthe mixture was concentrated
- additionThe residue was diluted with EtOAc
- washwashed with NaH2PO4 5%
- dry with materialThe organic layer was dried over MgSO4
- concentrationconcentrated
- customThe residue was purified by flash chromatography (Biotage SP1; column SNAP 50; TLC method: n-hexane/ethyl acetate 7/3; Rf=0.37)
Sources & evidence
- ORD record
- ord-ecdbe1098567436b989849284fbc01fd
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08119806B2
Reaction notes
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