Dimethylformamide → (S)-2,2-Difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)-1-(2-(5-((3,4,5-trimethoxyphenoxy)methyl)isoxazol-3-yl)pyrrolidin-1-yl)ethanone

HRID 710037Notes

Reaction equation

HRID 710037 reaction equation
CN(C=O)C.CS([O:10][CH2:11][C:12]1[O:16][N:15]=[C:14]([C@@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2[C:22](=[O:37])[C:23]([F:36])([F:35])[C:24]2([OH:34])[CH2:29][C:28]([CH3:31])([CH3:30])[CH2:27][C:26]([CH3:33])([CH3:32])[CH2:25]2)[CH:13]=1)(=O)=O.[CH3:38][O:39][C:40]1[CH:41]=[C:42](O)[CH:43]=[C:44]([O:48][CH3:49])[C:45]=1[O:46][CH3:47].C([O-])([O-])=O.[K+].[K+]>O>[F:35][C:23]([F:36])([C:24]1([OH:34])[CH2:29][C:28]([CH3:31])([CH3:30])[CH2:27][C:26]([CH3:33])([CH3:32])[CH2:25]1)[C:22]([N:18]1[CH2:19][CH2:20][CH2:21][C@H:17]1[C:14]1[CH:13]=[C:12]([CH2:11][O:10][C:42]2[CH:43]=[C:44]([O:48][CH3:49])[C:45]([O:46][CH3:47])=[C:40]([O:39][CH3:38])[CH:41]=2)[O:16][N:15]=1)=[O:37]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 695053,4,5-TrimethoxyphenolHCID 86706749HCID 86706749, compound

Product 1

HCID 73672155(S)-2,2-Difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)-1-(2-(5-((3,4,5-trimethoxyphenoxy)methyl)isoxazol-3-yl)pyrrolidin-1-yl)ethanoneYield 83.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a DMF (1.0 mL) solution of the compound (20.8 mg) obtained in Example 3-(5) and 3,4,5-trimethoxyphenol (16.0 mg), K2CO3 (24.0 mg) was added and the mixture was stirred at room temperature for 30 minutes, then at 50° C. for 2 hours. The reaction mixture was added to water (20 mL) and the organic layer extracted with AcOEt (20 mL×2) was dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by PTLC(NH-form) to give the titled compound (20.5 mg, colorless amorphous.)

Workup

  1. waitat 50° C. for 2 hours
  2. extractionthe organic layer extracted with AcOEt (20 mL×2)
  3. dry with materialwas dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude product, which
  7. customwas further purified by PTLC(NH-form)

Sources & evidence

ORD record
ord-48611e1c37c140a2b0751f9e1d79a5f4
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

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