Ammonium Chloride → HCID 86682448, compound

HRID 715905Notes

Reaction equation

HRID 715905 reaction equation
[F:1][C:2]1([F:56])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH:16]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=4)[CH2:15][C:14]([CH3:29])([CH3:28])[CH2:13][C:12]=3[N:11]=[C:10]([CH:30]3[CH2:35][CH2:34][N:33]([C:36]4[N:41]=[CH:40][C:39]([CH:42]=[O:43])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[CH:44]([F:55])[C:45]2[CH:50]=[CH:49][C:48]([C:51]([F:54])([F:53])[F:52])=[CH:47][CH:46]=2)[CH2:4][CH2:3]1.[CH2:57]([Mg]Br)[CH:58]([CH3:60])[CH3:59].O1CCCC1.[Cl-].[NH4+]>O1CCCC1>[F:56][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH:16]([O:18][CH2:19][C:20]4[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=4)[CH2:15][C:14]([CH3:28])([CH3:29])[CH2:13][C:12]=3[N:11]=[C:10]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]4[N:41]=[CH:40][C:39]([CH:42]([OH:43])[CH2:57][CH:58]([CH3:60])[CH3:59])=[CH:38][N:37]=4)[CH2:34][CH2:35]3)[C:9]=2[CH:44]([F:55])[C:45]2[CH:46]=[CH:47][C:48]([C:51]([F:53])([F:52])[F:54])=[CH:49][CH:50]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 866824324-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-formylpyrimidin-2-yl)piperidin-4-yl]-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinolineHCID 178420648HCID 178420648, compound2×

Product 1

HCID 86682448HCID 86682448, compoundYield 103.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 294 mg (0.377 mmol) of 4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-formylpyrimidin-2-yl)piperidin-4-yl]-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 16, in 5 ml of tetrahydrofuran, 0.5 ml (0.5 mmol) of 1.0 mol/L isobutylmagnesium bromide-tetrahydrofuran solution was added under an argon gas atmosphere, and the reaction solution was stirred at room temperature for 0.17 hour. Then, 1.0 ml (1.0 mmol) of 1.0 mol/L isobutylmagnesium bromide-tetrahydrofuran solution was further added thereto and the reaction solution was stirred at room temperature for 0.33 hour. After completion of the reaction, the reaction solution was poured into saturated ammonium chloride aqueous solution and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and then the solvent was distilled off under reduced pressure to provide 328 mg of the title compound as a foam (yield: quantitative).

Workup

  1. stirringthe reaction solution was stirred at room temperature for 0.33 hour
  2. customAfter completion of the reaction
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated sodium chloride aqueous solution
  5. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-9cd256b48d0746c7817d39b4fb1c97b9
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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