tert-Butanol → tert-Butyl (1-(trifluoromethyl)cyclobutyl)carbamate
Reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1(C(O)=O)[CH2:6][CH2:5][CH2:4]1.C([N:14]([CH2:17]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:20]C1C=CC=CC=1.[C:38]([OH:42])([CH3:41])([CH3:40])[CH3:39]>>[F:11][C:2]([F:1])([F:10])[C:3]1([NH:14][C:17](=[O:20])[O:42][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:4][CH2:5][CH2:6]1Participants
Procedure
1-(Trifluoromethyl)cyclobutanecarboxylic acid (1 g, 5.95 mmol) and triethylamine (0.912 mL, 6.54 mmol) in anhydrous tert-butanol (20 mL) was stirred at room temperature in the presence of 4 Å molecular sieves powder. To the mixture was added diphenyl phosphorazidate (1.801 g, 6.54 mmol). The reaction mixture was refluxed under N2 for 2 days, filtered, then concentrated in vacuo. The oily residue was stirred in ether, ether layer was isolated. The procedure was repeated three times. The combined organics were washed with 5% citric acid, saturated aqueous NaHCO3 twice, brine, dried over anhydrous Na2SO4, and concentrated to give tert-butyl 1-(trifluoromethyl)cyclobutylcarbamate (713 mg) as a white solid. The solid was dissolved in 1.25 N HCl in methanol solution (10 mL), stirred at 50° C. overnight, and concentrated to give the title compound (493 mg). 1H NMR (400 MHz, DMSO-d6) δ 1.87-1.97 (m, 1H), 2.04-2.15 (m, 1H), 2.44-2.50 (m, 4H), 9.40 (br, 3H).
Workup
- temperatureThe reaction mixture was refluxed under N2 for 2 days
- filtrationfiltered
- concentrationconcentrated in vacuo
- customether layer was isolated
- washThe combined organics were washed with 5% citric acid, saturated aqueous NaHCO3 twice
- dry with materialbrine, dried over anhydrous Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-b18eda383fec4fd3b057ecf22b0e8558
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08778950B2
Reaction notes
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