tert-Butanol → t-Butyl 4-(1-methylpiperidine-4-yloxy)-3-(trifluoromethyl)phenylcarbamate

HRID 1465010Notes

Reaction equation

HRID 1465010 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9]2[CH:17]=[CH:16][C:12](C(O)=O)=[CH:11][C:10]=2[C:18]([F:21])([F:20])[F:19])[CH2:4][CH2:3]1.C1C=CC(P([N:36]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[C:39]([O-:42])(O)=[O:40].[Na+].[CH3:44][C:45](O)([CH3:47])[CH3:46]>>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([O:8][C:9]2[CH:17]=[CH:16][C:12]([NH:36][C:39](=[O:40])[O:42][C:45]([CH3:47])([CH3:46])[CH3:44])=[CH:11][C:10]=2[C:18]([F:19])([F:20])[F:21])[CH2:6][CH2:7]1

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 199401P,P-Diphenylphosphinic azideHCID 516892Sodium BicarbonateHCID 23145857HCID 23145857, compound

Product 1

HCID 67359882t-Butyl 4-(1-methylpiperidine-4-yloxy)-3-(trifluoromethyl)phenylcarbamateYield 45%

Conditions

Temperature
90 °C

Procedure

4-(1-Methylpiperidine-4-yloxy)-3-(trifluoromethyl)benzoic acid (200 mg, 0.659 mmol) was dissolved in t-BuOH (6 mL) and then DPPA (0.21 mL, 0.989 mmol) and TEA (0.14 mL, 0.989 mmol) was added thereto. The reaction mixture was stirred at 90° C. for 23 hours, cooled to room temperature, and sat. NaHCO3 solution was added thereto. The aqueous layer was washed with ethyl acetate, and the combined organic layer was dried with Na2SO4, filtered and concentrated. The resulting mixture was purified by silica gel chromatography (DCM/MeOH=10/1) to obtain the title compound (82 mg, 45%).

Workup

  1. temperaturecooled to room temperature
  2. washThe aqueous layer was washed with ethyl acetate
  3. dry with materialthe combined organic layer was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting mixture was purified by silica gel chromatography (DCM/MeOH=10/1)

Sources & evidence

ORD record
ord-eb30cf0afab14257b0b58e0655b657b1
Source dataset
uspto-grants-2015_04
Patent number
US08999973B2

Reaction notes

Loading…