Water → HCID 89683078, compound

HRID 632605Notes

Reaction equation

HRID 632605 reaction equation
[Si]([O:8][C:9]1[CH:10]=[N:11][C:12]([N:15]2[CH2:20][CH2:19][CH:18]([C:21]3[C:30]([C@@H:31]([F:42])[C:32]4[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=4)=[C:29]([CH:43]4[CH2:48][CH2:47][C:46]([F:50])([F:49])[CH2:45][CH2:44]4)[C:28]4[C@@H:27]([O:51][CH2:52][C:53]5[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=5)[CH2:26][C:25]([CH3:62])([CH3:61])[CH2:24][C:23]=4[N:22]=3)[CH2:17][CH2:16]2)=[N:13][CH:14]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.O>O1CCCC1>[F:50][C:46]1([F:49])[CH2:47][CH2:48][CH:43]([C:29]2[C:28]3[C@@H:27]([O:51][CH2:52][C:53]4[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=4)[CH2:26][C:25]([CH3:62])([CH3:61])[CH2:24][C:23]=3[N:22]=[C:21]([CH:18]3[CH2:17][CH2:16][N:15]([C:12]4[N:13]=[CH:14][C:9]([OH:8])=[CH:10][N:11]=4)[CH2:20][CH2:19]3)[C:30]=2[C@@H:31]([F:42])[C:32]2[CH:33]=[CH:34][C:35]([C:38]([F:39])([F:41])[F:40])=[CH:36][CH:37]=2)[CH2:44][CH2:45]1

Participants

6

Reactant 4

HCID 962WaterHCID 1140TolueneHCID 2724141Tetrabutylammonium FluorideHCID 131735437(5S)-2-(1-{5-[(tert-Butyldimethylsilyl)oxy]pyrimidin-2-yl}piperidin-4-yl)-4-(4,4-difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline

Product 1

HCID 89683078HCID 89683078, compoundYield 99.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1.00 g (1.13 mmol) of (5S)-2-(1-{5-[(tert-Butyldimethylsilyl)oxy]pyrimidin-2-yl}piperidin-4-yl)-4-(4,4-difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 13, in 2 ml of tetrahydrofuran, 1.5 ml of a solution of 1.0 M tetra-n-butylammonium fluoride in tetrahydrofuran was added, and the reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, toluene and water were added to the reaction solution to separate an organic phase. Further, the reaction mixture was extracted with toluene from the aqueous phase. The obtained organic phases were combined and washed with saturated sodium chloride aqueous solution, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=78/22-55/45 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 861 mg of the title compound as a white solid (yield: 99%).

Workup

  1. additionwere added to the reaction solution
  2. customto separate an organic phase
  3. extractionFurther, the reaction mixture was extracted with toluene from the aqueous phase
  4. washwashed with saturated sodium chloride aqueous solution
  5. distillationthe solvent was distilled off under reduced pressure
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-57da7581244b4bf48b3bf5cd1ecf2b03
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

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