Lithium hydroxide, monohydrate → Lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetate

HRID 1473146Notes

Reaction equation

HRID 1473146 reaction equation
O[Li:2].O.C[O:5][C:6](=[O:46])[CH2:7][C:8]1[C:9]([CH2:14][CH2:15][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([CH:33]4[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]4)=[CH:29][CH:28]=3)[N:17]=2)=[N:10][CH:11]=[CH:12][CH:13]=1>C1COCC1.O.CO>[C:42]([O:41][C:39]([N:36]1[CH2:35][CH2:34][CH:33]([C:30]2[CH:31]=[CH:32][C:27]([NH:26][C:18]3[N:17]=[C:16]([CH2:15][CH2:14][C:9]4[C:8]([CH2:7][C:6]([O-:46])=[O:5])=[CH:13][CH:12]=[CH:11][N:10]=4)[C:21]([C:22]([F:23])([F:24])[F:25])=[CH:20][N:19]=3)=[CH:28][CH:29]=2)[CH2:38][CH2:37]1)=[O:40])([CH3:45])([CH3:43])[CH3:44].[Li+:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71208998tert-Butyl 4-(4-((4-(2-(3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 71209298Lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetateYield 91%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiOH.H2O (19.1 mg, 0.455 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I122) (90.9 mg, 0.152 mmol) in THF (7 mL), water (1.5 mL) and methanol (1 mL). The resulting mixture was allowed to stir at room temperature for 20 hours. The volatiles were removed in vacuo and the residue was diluted with EtOAc (50 mL) and sat. aq. NaHCO3 (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL), the organic layers were combined, washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound (I123) (81.3 mg, 91%) as a pale yellow viscous oil.

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (50 mL) and sat. aq. NaHCO3 (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  5. washwashed with brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a45ede4c09a7448eb20bc8e2c7561d26
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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