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

HRID 1485155Notes

Reaction equation

HRID 1485155 reaction equation
O[Li:2].O.C[O:5][C:6](=[O:46])[CH2:7][C:8]1[CH:45]=[CH:44][CH:43]=[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][CH2:32][N:31]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:30]3)=[CH:25][CH:24]=2)[N:13]=1>C1COCC1.O.CO>[C:38]([O:37][C:35]([N:31]1[CH2:32][CH2:33][CH2:34][CH:29]([C:26]2[CH:25]=[CH:24][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:9]4[CH:42]=[CH:43][CH:44]=[CH:45][C:8]=4[CH2:7][C:6]([O-:46])=[O:5])[C:17]([C:18]([F:20])([F:19])[F:21])=[CH:16][N:15]=3)=[CH:28][CH:27]=2)[CH2:30]1)=[O:36])([CH3:41])([CH3:39])[CH3:40].[Li+:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71209222tert-Butyl 3-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 68282896Lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetateYield 101.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

LiOH.H2O (0.052 g, 1.25 mmol) was added to tert-butyl 3-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I26) (0.249 g, 0.416 mmol) in THF (10 mL), water (2.5 mL) and methanol (1 mL). The resulting mixture was allowed to stir for 2 hours at 40° C. and then 20 hours at room temperature. The volatiles were removed in vacuo and the residue was diluted with EtOAc (70 mL) and 2 M aq. NaOH (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (70 mL), the organic layers were combined, washed with brine (70 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the title compound (I27) (0.250 g, 100% yield) as an off-white oily solid; 1H NMR (400 MHz, d6-DMSO) δ 10.23 (s, 1H), 8.64 (s, 1H), 7.72-7.60 (m, 2H), 7.25-7.00 (m, 6H), 4.01-3.88 (m, 2H), 3.48 (s, 2H), 3.13-2.92 (m, 4H), 2.86-2.63 (m, 2H), 1.91-1.81 (m, 1H), 1.72-1.54 (m, 2H), 1.48-1.34 (m, 10H). LCMS Method C: rt 6.71 min; m/z 585.3 [M+H]+.

Workup

  1. custom20 hours
  2. customat room temperature
  3. customThe volatiles were removed in vacuo
  4. additionthe residue was diluted with EtOAc (70 mL) and 2 M aq. NaOH (50 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (70 mL)
  7. washwashed with brine (70 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3106af84d1b24e498d58c72fdc749d20
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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