1-Butanol → HCID 178451792, compound

HRID 1685140Notes

Reaction equation

HRID 1685140 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=O)[NH:15][CH2:16][C:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=2)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)CCC.C([O-])(=O)C.[NH4+:40]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)[N:40]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 2631-ButanolHCID 517165Ammonium AcetateHCID 534391291-Boc-4-(2-(4-Fluoro-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)piperidine

Product 1

HCID 178451792HCID 178451792, compoundYield 64.9%

Conditions

Temperature
160 °C

Procedure

To a solution of 4-(2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester (29.4 g; 1.00 equiv; 67.99 mmol) in 1-butanol (150 mL; 1.64 mol), add ammonium acetate (15 equiv; 1.02 mol; 78.61 g) followed by TEA (1 equiv; 67.99 mmol; 9.48 mL). Stir the mixture at 160° C. in a sealed tube. After 3 h, cool to RT and partition between EA and water and wash the organic layer with water and brine. Concentrate in vacuo. Triturate the residue in MTBE, filter and dry in vacuo to give the title compound (18.23 g; 44.10 mmol; 64.86%) as a white solid. 1H NMR (300 MHz, DMSO): 12.01 (s, 1H), 8.08-8.04 (m, 2H), 7.70 (d, J=1.4 Hz, 1H), 7.49-7.43 (m, 1H), 3.99 (d, J=12.6 Hz, 2H), 2.92-2.85 (m, 3H), 1.91-1.87 (m, 2H), 1.64-1.51 (m, 2H), 1.41 (s, 9H).

Workup

  1. temperaturecool to RT
  2. custompartition between EA and water
  3. washwash the organic layer with water and brine
  4. concentrationConcentrate in vacuo
  5. customTriturate the residue in MTBE
  6. filtrationfilter
  7. customdry in vacuo

Sources & evidence

ORD record
ord-97ecd0bfcd4c4b3b8b546b720db17da6
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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