Toluene → (R)-2-(4-(9-Hydroxy-2-(3-hydroxy-3-methylbutoxy)-9-(trifluoromethyl)-9H-fluoren-4-yl)-1H-pyrazol-1-yl)-2-methylpropanamide

HRID 579391Notes

Reaction equation

HRID 579391 reaction equation
O.[OH:2][C@@:3]1([C:34]([F:37])([F:36])[F:35])[C:15]2[CH:14]=[C:13]([O:16][CH2:17][CH2:18][C:19]([OH:22])([CH3:21])[CH3:20])[CH:12]=[C:11]([C:23]3[CH:24]=[N:25][N:26]([C:28]([CH3:33])([CH3:32])[C:29]([NH2:31])=[O:30])[CH:27]=3)[C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2.C1(C)C=CC=CC=1>O>[OH:2][C@@:3]1([C:34]([F:36])([F:37])[F:35])[C:15]2[CH:14]=[C:13]([O:16][CH2:17][CH2:18][C:19]([OH:22])([CH3:20])[CH3:21])[CH:12]=[C:11]([C:23]3[CH:24]=[N:25][N:26]([C:28]([CH3:32])([CH3:33])[C:29]([NH2:31])=[O:30])[CH:27]=3)[C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2

Participants

4

Reactant 2

HCID 1140TolueneHCID 783249482-{4-[(9R)-9-Hydroxy-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide monohydrate2×

Product 1

HCID 78210288(R)-2-(4-(9-Hydroxy-2-(3-hydroxy-3-methylbutoxy)-9-(trifluoromethyl)-9H-fluoren-4-yl)-1H-pyrazol-1-yl)-2-methylpropanamideYield 98.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

To 2-{4-[(9R)-9-hydroxy-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide monohydrate (compound (2h)) (22.63 g) obtained in the previous step was added toluene (340 ml). The reaction mixture was stirred at an oil bath temperature of 130° C. for 2 hr under a nitrogen atmosphere with removing water by a Dean-Stark apparatus. The reaction mixture was further stirred at an oil bath temperature of 70° C. for 1.5 hr, allowed to cool to room temperature, and stirred overnight. The precipitated solid was collected by filtration, and washed with toluene (100 ml). The obtained solid was dried under reduced pressure at room temperature for 3 days, and further dried under reduced pressure at 60° C. for 1 day to give the title compound (21.5 g).

Workup

  1. temperatureto cool to room temperature
  2. stirringstirred overnight
  3. filtrationThe precipitated solid was collected by filtration
  4. washwashed with toluene (100 ml)
  5. customThe obtained solid was dried under reduced pressure at room temperature for 3 days
  6. customfurther dried under reduced pressure at 60° C. for 1 day

Sources & evidence

ORD record
ord-e440545073bf4d8a80a0746d053cf84f
Source dataset
uspto-grants-2015_05
Patent number
US09040717B2

Reaction notes

Loading…