Ammonium Chloride → (S)-2,2-Difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)-1-(2-(5-(hydroxymethyl)isoxazol-3-yl)pyrrolidin-1-yl)ethanone

HRID 710035Notes

Reaction equation

HRID 710035 reaction equation
[Si]([O:18][CH2:19][C:20]1[O:24][N:23]=[C:22]([C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:30](=[O:45])[C:31]([F:44])([F:43])[C:32]2([OH:42])[CH2:37][C:36]([CH3:39])([CH3:38])[CH2:35][C:34]([CH3:41])([CH3:40])[CH2:33]2)[CH:21]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-].[NH4+].[Cl-]>C1COCC1>[F:44][C:31]([F:43])([C:32]1([OH:42])[CH2:33][C:34]([CH3:41])([CH3:40])[CH2:35][C:36]([CH3:39])([CH3:38])[CH2:37]1)[C:30]([N:26]1[CH2:27][CH2:28][CH2:29][C@H:25]1[C:22]1[CH:21]=[C:20]([CH2:19][OH:18])[O:24][N:23]=1)=[O:45]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 86706748HCID 86706748, compound

Product 1

HCID 86706747(S)-2,2-Difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)-1-(2-(5-(hydroxymethyl)isoxazol-3-yl)pyrrolidin-1-yl)ethanoneYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a THF (20 mL) solution of the compound (1.784 g) obtained in Example 3-(3), n-Bu4NF (3.4 mL, 1.0 M THF solution) was added and the mixture was stirred at room temperature for 20 minutes. To the reaction mixture, a saturated aqueous solution of NH4Cl was added and the organic layer extracted with AcOEt was dried (MgSO4), filtered and concentrated to give a crude product, which was further purified with neutral silica gel chromatography (AcOEt/hexane) to give the titled compound (1.010 g, colorless solid.)

Workup

  1. extractionthe organic layer extracted with AcOEt
  2. dry with materialwas dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a crude product, which
  6. customwas further purified with neutral silica gel chromatography (AcOEt/hexane)

Sources & evidence

ORD record
ord-74c5672814ba4780a9cf8f1ec767883e
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

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