Water → HCID 10281878, compound

HRID 1860964Notes

Reaction equation

HRID 1860964 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:11]=[CH:10][C:9]=1[NH:20][CH3:21].C(N(CC)CC)C.[F:29][C:30]([F:48])([F:47])[C:31]1[CH:32]=[C:33]([C:41]([CH3:46])([CH3:45])[C:42](Cl)=[O:43])[CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1.O>ClCCl>[F:39][C:37]([F:40])([F:38])[C:35]1[CH:34]=[C:33]([C:41]([CH3:46])([CH3:45])[C:42]([N:20]([C:9]2[CH:10]=[N:11][C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[CH:13][C:8]=2[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[CH3:21])=[O:43])[CH:32]=[C:31]([C:30]([F:48])([F:29])[F:47])[CH:36]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 112671412-(3,5-Bis(trifluoromethyl)phenyl)-2-methylpropanoyl chlorideHCID 18624484HCID 18624484, compound

Product 1

HCID 10281878HCID 10281878, compoundYield 86.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

8.56 g (28.1 mmol) [4-(2-Chloro-phenyl)-6-morpholin-4-yl-pyridin-3-yl]-methyl-amine were dissolved in 50 ml dichloromethane in the presence of 5.5 ml (1.4 eq.) triethylamine and cooled to 0° C. A solution of 10.8 g (1.05 eq.) 2-(3,5-bistrifluoromethyl-phenyl)-2-methyl-propionyl chloride (step a) in 10 ml dichloromethane was added slowly and after 2 hours, 80 ml water was added. After 15 minutes stirring, the phases were separated, the aqueous phase was extracted with 2 portions of 80 ml dichloromethane and the combined organic extracts were washed with 80 ml water, 80 ml 2% aqueous NaOH, 80 ml water and 80 ml 5% aqueous NaHCO3, dried over Na2SO4 and concentrated under reduced pressure. Crystallization from 40 ml 2-propanol and 20 ml ethanol at −20° C. yielded 14.2 g (86%) of 2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(2-chloro-phenyl)-6-morpholin-4-yl-pyridin-3-yl]-N-methyl-isobutyramide as a white powder of m.p.=134.4-135.5° C.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with 2 portions of 80 ml dichloromethane
  3. washthe combined organic extracts were washed with 80 ml water, 80 ml 2% aqueous NaOH, 80 ml water and 80 ml 5% aqueous NaHCO3
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customCrystallization from 40 ml 2-propanol and 20 ml ethanol at −20° C.

Sources & evidence

ORD record
ord-ac3b854e9a334ad8a88c76adeb87522c
Source dataset
uspto-grants-2003_03
Patent number
US06531597B2

Reaction notes

Loading…