Triethylamine → (S)-1-(2-(5-((3,4-Dimethoxyphenoxy)methyl)oxazol-2-yl)pyrrolidin-1-yl)-2,2-difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)ethanone

HRID 710066Notes

Reaction equation

HRID 710066 reaction equation
[F:1][C:2]([F:17])([C:6]1([OH:16])[CH2:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8]([CH3:15])([CH3:14])[CH2:7]1)[C:3]([OH:5])=O.CCN(CC)CC.ClC(OCC)=O.[CH3:31][O:32][C:33]1[CH:34]=[C:35]([CH:48]=[CH:49][C:50]=1[O:51][CH3:52])[O:36][CH2:37][C:38]1[O:42][C:41]([C@@H:43]2[CH2:47][CH2:46][CH2:45][NH:44]2)=[N:40][CH:39]=1>C1COCC1.O>[CH3:31][O:32][C:33]1[CH:34]=[C:35]([CH:48]=[CH:49][C:50]=1[O:51][CH3:52])[O:36][CH2:37][C:38]1[O:42][C:41]([C@@H:43]2[CH2:47][CH2:46][CH2:45][N:44]2[C:3](=[O:5])[C:2]([F:1])([F:17])[C:6]2([OH:16])[CH2:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8]([CH3:15])([CH3:14])[CH2:7]2)=[N:40][CH:39]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 68542826Difluoro(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acidHCID 86706779(S)-5-((3,4-Dimethoxyphenoxy)methyl)-2-(pyrrolidin-2-yl)oxazole

Product 1

HCID 73672159(S)-1-(2-(5-((3,4-Dimethoxyphenoxy)methyl)oxazol-2-yl)pyrrolidin-1-yl)-2,2-difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)ethanoneYield 78.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2,2-difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acid (0.075 g) and Et3N (0.038 ml) in THF (1 ml), ethyl chloroformate (0.028 g) was added over an ice bath, followed by stirring at the same temperature for an hour. To the reaction mixture, a solution of (S)-5-((3,4-dimethoxyphenoxy)methyl)-2-(pyrrolidin-2-yl)oxazole (0.075 g) in THF (1 ml) was added over an ice bath, followed by stirring at room temperature for 15 hours. After adding water and performing extraction with AcOEt, the organic layer was washed with saturated aqueous sodium chloride, dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by silica gel chromatography (AcOEt/hexane) to give the titled compound (0.104 g, colorless amorphous.)

Workup

  1. stirringby stirring at room temperature for 15 hours
  2. extractionextraction with AcOEt
  3. washthe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas further purified by silica gel chromatography (AcOEt/hexane)

Sources & evidence

ORD record
ord-d34b9195f4424485a4d38b65d69a6214
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

Loading…