Tetrahydrofuran → HCID 86620349, compound
Reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C(N(C(C)C)CC)(C)C.[NH2:24][CH:25]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[C:26]([O:28][CH3:29])=[O:27].[O:37]1CCC[CH2:38]1>>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([NH:1][C:38]([NH:24][CH:25]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[C:26]([O:28][CH3:29])=[O:27])=[O:37])[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1Participants
Procedure
4-Amino-1-benzylpiperidine (460 mg, 2.42 mmol) in tetrahydrofuran (15 mL) was added to a solution of p-nitrophenylchloroformate (487 mg, 2.42 mmol) and diisopropylethylamine (430 uL, 2.42 mmol) in tetrahydrofuran (5 mL) at 0° C. After 1 h, additional diisopropylethylamine was added (860 uL, 4.84 mmol) along with methyl amino(4-fluorophenyl)acetate (443 mg, 2.42 mmol). The reaction was warmed to room temperature and stirred overnight. The mixture was filtered, concentrated and redissolved in ethyl acetate. The ethyl acetate layer was washed with 1N sodium hydroxide (3×), saturated sodium bicarbonate solution, water, brine, and dried over sodium sulfate. The crude product was purified by column chromatography (silica gel, 0 to 5%/methanol in methylene chloride gradient elution), giving the title compound (700 mg). MS 400.29 (M+1)
Workup
- filtrationThe mixture was filtered
- concentrationconcentrated
- dissolutionredissolved in ethyl acetate
- washThe ethyl acetate layer was washed with 1N sodium hydroxide (3×), saturated sodium bicarbonate solution, water, brine
- dry with materialdried over sodium sulfate
- customThe crude product was purified by column chromatography (silica gel, 0 to 5%/methanol in methylene chloride gradient elution)
Sources & evidence
- ORD record
- ord-bd5ed33b45a44d8a898e8cce4a1db195
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07632832B2
Reaction notes
Loading…