Acetonitrile → (S)-1-(2-(5-((Dimethylamino)methyl)isoxazol-3-yl)pyrrolidin-1-yl)-2,2-difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)ethanone

HRID 710038Notes

Reaction equation

HRID 710038 reaction equation
CS(O[CH2:6][C:7]1[O:11][N:10]=[C:9]([C@@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[C:17](=[O:32])[C:18]([F:31])([F:30])[C:19]2([OH:29])[CH2:24][C:23]([CH3:26])([CH3:25])[CH2:22][C:21]([CH3:28])([CH3:27])[CH2:20]2)[CH:8]=1)(=O)=O.C1COCC1.[CH3:38]COC(C)=O.C[C:45]#[N:46]>>[CH3:38][N:46]([CH2:6][C:7]1[O:11][N:10]=[C:9]([C@@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[C:17](=[O:32])[C:18]([F:30])([F:31])[C:19]2([OH:29])[CH2:24][C:23]([CH3:25])([CH3:26])[CH2:22][C:21]([CH3:28])([CH3:27])[CH2:20]2)[CH:8]=1)[CH3:45]

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 86706749HCID 86706749, compound

Product 1

HCID 73672156(S)-1-(2-(5-((Dimethylamino)methyl)isoxazol-3-yl)pyrrolidin-1-yl)-2,2-difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)ethanone

Procedure

The compound (160 mg) obtained in Example 3-(5) was dissolved in MeCN and after adding a THF solution of dimethyllamine (2 M, 250 μL), the mixture was stirred at room temperature for 3 hours. To the reaction mixture, AcOEt (50 ml) and a saturated aqueous solution of NaCO3 (50 ml) were added to separate the organic layer. The resulting organic layer was washed with brine (50 ml), 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 (83 mg, colorless amorphous.)

Workup

  1. customto separate the organic layer
  2. washThe resulting organic layer was washed with brine (50 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude product, which
  7. customwas further purified by silica gel chromatography (AcOEt/hexane)

Sources & evidence

ORD record
ord-6bcebc64d7a64470aa40ec0ac8e1962a
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

Loading…