Lithium hydroxide, monohydrate → HCID 86712695, compound

HRID 1779051Notes

Reaction equation

HRID 1779051 reaction equation
O[Li].O.C[O:5][C:6](=[O:47])[CH2:7][C:8]1[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][C:9]=1[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[N:13]=1>C1COCC1.O.CO>[C:38]([O:37][C:35]([N:32]1[CH2:33][CH2:34][CH:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:9]4[CH:42]=[C:43]([CH3:46])[CH:44]=[CH:45][C:8]=4[CH2:7][C:6]([OH:47])=[O:5])[C:17]([C:18]([F:20])([F:19])[F:21])=[CH:16][N:15]=3)=[CH:24][CH:25]=2)[CH2:30][CH2:31]1)=[O:36])([CH3:41])([CH3:39])[CH3:40]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86712696HCID 86712696, compound

Product 1

HCID 86712695HCID 86712695, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiOH.H2O (0.028 g, 0.65 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)-5-methylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A88) (0.133 g, 0.217 mmol) in THF (7 mL), water (1.5 mL) and MeOH (1 mL) and the resulting mixture stirred at room temperature for 27 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4 and the volatiles removed in vacuo to give the title compound A89 as a white solid (0.124 g, 95%); 1H NMR (400 MHz, d4-MeOH) δ 8.49 (s, 1H), 7.61 (d, J=8.5 Hz, 2H), 7.15 (d, J=8.5 Hz, 2H), 7.09 (d, J=7.7 Hz, 1H), 7.00 (s, 1H), 6.96 (d, J=7.7 Hz, 1H), 4.18 (d, J=13.1 Hz, 2H), 3.65 (s, 2H), 3.13-2.90 (m, 4H), 2.92-2.71 (m, 2H), 2.64 (tt, J=12.0, 3.1 Hz, 1H), 2.26 (s, 3H), 1.78 (d, J=12.5 Hz, 2H), 1.61-1.49 (m, 2H), 1.47 (s, 9H). LCMS-A: rt 6.736 min; m/z 599.3 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  5. washThe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-008df0984aea4f47aae253816bc81a84
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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