Water → HCID 178520948, compound

HRID 2406790Notes

Reaction equation

HRID 2406790 reaction equation
[H-].[Na+].[F:3][C:4]([F:21])([F:20])[C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]([N:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[CH2:18][OH:19])=[O:12])[CH2:7][CH2:6]1.Br[C:23]1[CH:24]=[N:25][CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1.O>CS(C)=O>[F:30][C:29]([F:32])([F:31])[C:27]1[CH:26]=[N:25][CH:24]=[C:23]([O:19][CH2:18][C@H:14]2[CH2:15][CH2:16][CH2:17][N:13]2[C:11]([C@H:8]2[CH2:7][CH2:6][C@H:5]([C:4]([F:3])([F:20])[F:21])[CH2:10][CH2:9]2)=[O:12])[CH:28]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 111279913-Bromo-5-(trifluoromethyl)pyridineHCID 178520946HCID 178520946, compound

Product 1

HCID 178520948HCID 178520948, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

NaH (60% oil dispersant, 11 mg, 0.27 mmol) was placed on the reaction tube, and a solution of [(2R)-1-{[trans-4-(trifluoromethyl)cyclohexyl]carbonyl}pyrrolidin-2-yl]methanol (68 mg, 0.24 mmol, EXAMPLE 31 Step 1) in DMSO (2.0 mL) was added at ambient temperature. After being stirred for 15 min at room temperature, 3-bromo-5-(trifluoromethyl)pyridine (50 mg, 0.22 mmol) was added to the mixture at ambient temperature. The mixture was heated stepwise with continuous stirring, at room temperature for 19 h, at 50° C. for 3 h, at 80° C. for 15 h, and at 100° C. for 15 h. After cooling to room temperature, water was added to the mixture. The mixture was extracted with ethyl acetate twice and washed with brine. The extracts were combined and dried over sodium sulfate and concentrated in vacuo to give an oil. The residual oil was purified by silica gel preparative thin layer chromatography (TLC) (ethyl acetate/hexane 3:2) to afford 40 mg (43%) of the title compound as a colorless viscous oil.

Workup

  1. temperatureThe mixture was heated stepwise with continuous stirring, at room temperature for 19 h, at 50° C. for 3 h, at 80° C. for 15 h
  2. waitat 100° C. for 15 h
  3. temperatureAfter cooling to room temperature
  4. extractionThe mixture was extracted with ethyl acetate twice
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto give an oil
  9. customThe residual oil was purified by silica gel preparative thin layer chromatography (TLC) (ethyl acetate/hexane 3:2)

Sources & evidence

ORD record
ord-84cdbcd4bf0048388a4652ad48e7b66b
Source dataset
uspto-grants-2014_08
Patent number
US08809380B2

Reaction notes

Loading…