Water → 2-{4-[(9R)-9-Hydroxy-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide monohydrate

HRID 579390Notes

Reaction equation

HRID 579390 reaction equation
[OH:1][C@@:2]1([C:33]([F:36])([F:35])[F:34])[C:14]2[CH:13]=[C:12]([O:15][CH2:16][CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])[CH:11]=[C:10]([C:22]3[CH:23]=[N:24][N:25]([C:27]([CH3:32])([CH3:31])[C:28]([NH2:30])=[O:29])[CH:26]=3)[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.O.CCCCCC>C(OCC)(=O)C>[OH2:1].[OH:1][C@@:2]1([C:33]([F:35])([F:36])[F:34])[C:14]2[CH:13]=[C:12]([O:15][CH2:16][CH2:17][C:18]([OH:21])([CH3:19])[CH3:20])[CH:11]=[C:10]([C:22]3[CH:23]=[N:24][N:25]([C:27]([CH3:31])([CH3:32])[C:28]([NH2:30])=[O:29])[CH:26]=3)[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2

Participants

5

Reactant 3

HCID 962WaterHCID 8058Hexane2×HCID 78210288(R)-2-(4-(9-Hydroxy-2-(3-hydroxy-3-methylbutoxy)-9-(trifluoromethyl)-9H-fluoren-4-yl)-1H-pyrazol-1-yl)-2-methylpropanamide2×

Product 1

HCID 783249482-{4-[(9R)-9-Hydroxy-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide monohydrateYield 168%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
50 °C

Procedure

2-{4-[(9R)-9-Hydroxy-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (compound (2)) (60.0 g) obtained in the previous step was dissolved in ethyl acetate (109 ml), water (2 ml) was added, and the mixture was heated to 50° C. To this mixture were successively added dropwise hexane (226 ml), and a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate 2:1, 150 ml), and the mixture was allowed to cool to room temperature and stirred overnight. The precipitated solid was collected by filtration, and washed with a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=2:1, 180 ml). The obtained solid was dried under reduced pressure at room temperature overnight to give the title compound (52.2 g, optical purity 98.6% e.e.). The optical purity was determined under the HPLC analysis condition 2. Retention time of (R) form 11.3 min, retention time of (S) form 13.9 min. Specific optical rotation [α]p+37.9° (c=1.01 MeOH 25° C.)

Workup

  1. temperatureto cool to room temperature
  2. filtrationThe precipitated solid was collected by filtration
  3. washwashed with a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=2:1, 180 ml)
  4. customThe obtained solid was dried under reduced pressure at room temperature overnight

Sources & evidence

ORD record
ord-5ac310b48c1148cfa0c62f8acbc224e6
Source dataset
uspto-grants-2015_05
Patent number
US09040717B2

Reaction notes

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