Lithium hydroxide, monohydrate → Lithium 2-(4-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoro-methyl)pyrimidin-4-yl)ethyl)pyrimidin-5-yl)acetate

HRID 1473134Notes

Reaction equation

HRID 1473134 reaction equation
O[Li:2].O.C([O:6][C:7](=[O:47])[CH2:8][C:9]1[C:10]([CH2:15][CH2:16][C:17]2[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([CH:34]4[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]4)=[CH:30][CH:29]=3)[N:18]=2)=[N:11][CH:12]=[N:13][CH:14]=1)C>C1COCC1.O.CO>[C:43]([O:42][C:40]([N:37]1[CH2:36][CH2:35][CH:34]([C:31]2[CH:30]=[CH:29][C:28]([NH:27][C:19]3[N:18]=[C:17]([CH2:16][CH2:15][C:10]4[C:9]([CH2:8][C:7]([O-:47])=[O:6])=[CH:14][N:13]=[CH:12][N:11]=4)[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=3)=[CH:33][CH:32]=2)[CH2:39][CH2:38]1)=[O:41])([CH3:46])([CH3:44])[CH3:45].[Li+:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71209322tert-Butyl 4-(4-((4-(2-(5-(2-ethoxy-2-oxoethyl)pyrimidin-4-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 71209343Lithium 2-(4-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoro-methyl)pyrimidin-4-yl)ethyl)pyrimidin-5-yl)acetateYield 103.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiOH.H2O (0.020 g, 0.468 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(5-(2-ethoxy-2-oxoethyl)pyrimidin-4-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I112) (0.096 g, 0.156 mmol) in THF (7 mL), water (1.5 mL) and methanol (1 mL) and the resulting mixture was allowed to stir at room temperature for 18 hours. The volatiles were removed in vacuo and the residue was diluted with EtOAc (70 mL) and 2 M aqueous NaOH (80 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×70 mL), the combined organics were washed with brine (70 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the title compound (I113) (0.096 g, quantitative) as a pale yellow solid. LCMS Method C: rt 6.19 min; m/z 587.1 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (70 mL) and 2 M aqueous NaOH (80 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×70 mL)
  5. washthe combined organics were washed with brine (70 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-464b15f14aa641feb3417ddc2e7cea19
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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