tert-Butanol → tert-Butyl {1-[(4-cyanopiperidin-1-yl)carbonyl]-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}carbamate

HRID 876262Notes

Reaction equation

HRID 876262 reaction equation
C([N:3]([CH2:6]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:9]C1C=CC=CC=1.[C:27]([CH:29]1[CH2:34][CH2:33][N:32]([C:35]([N:37]2[CH2:42][CH:41]([C:43]3[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][CH:44]=3)[CH2:40][CH:39](C(O)=O)[CH2:38]2)=[O:36])[CH2:31][CH2:30]1)#[N:28].[C:56]([OH:60])([CH3:59])([CH3:58])[CH3:57]>>[C:27]([CH:29]1[CH2:30][CH2:31][N:32]([C:35]([N:37]2[CH2:42][CH:41]([C:43]3[CH:44]=[CH:45][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:47][CH:48]=3)[CH2:40][CH:39]([NH:3][C:6](=[O:9])[O:60][C:56]([CH3:59])([CH3:58])[CH3:57])[CH2:38]2)=[O:36])[CH2:33][CH2:34]1)#[N:28]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 580023321-[(4-Cyanopiperidin-1-yl)carbonyl]-5-[4-(trifluoromethyl)phenyl]piperidine-3-carboxylic acid

Product 1

HCID 68075239tert-Butyl {1-[(4-cyanopiperidin-1-yl)carbonyl]-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}carbamate

Procedure

18 g of molecular sieves 4 Å, 3.2 ml (2.3 g, 23 mmol) of triethylamine and 4.6 ml (5.8 g, 21 mmol) of diphenyl phosphorazidate were added to a solution of 7.90 g (19.3 mmol) of the carboxylic acid from Example 67A in 350 ml of tert-butanol, and the mixture was stirred under reflux overnight. The molecular sieves were then filtered off and washed repeatedly with ethyl acetate, and the filtrate was concentrated under reduced pressure. The residue was taken up in ethyl acetate and then washed with 2N hydrochloric acid, saturated aqueous sodium bicarbonate solution and water. The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. Yield: 8.34 g with a purity of 91% (82% of theory)

Workup

  1. temperatureunder reflux overnight
  2. filtrationThe molecular sieves were then filtered off
  3. washwashed repeatedly with ethyl acetate
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. washwashed with 2N hydrochloric acid, saturated aqueous sodium bicarbonate solution and water
  6. dry with materialThe organic phase was dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0f98353475784f6bad77e469670d5e01
Source dataset
uspto-grants-2015_03
Patent number
US08987248B2

Reaction notes

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