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

HRID 1485164Notes

Reaction equation

HRID 1485164 reaction equation
O[Li:2].O.C[O:5][C:6]([C:8]1[CH:9]=[C:10]([CH:43]=[CH:44][CH:45]=1)[CH2:11][CH2:12][C:13]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[CH:26][CH:25]=2)[N:14]=1)=[O:7]>C1COCC1.O.CO>[C:39]([O:38][C:36]([N:33]1[CH2:34][CH2:35][N:30]([C:27]2[CH:26]=[CH:25][C:24]([NH:23][C:15]3[N:14]=[C:13]([CH2:12][CH2:11][C:10]4[CH:9]=[C:8]([CH:45]=[CH:44][CH:43]=4)[C:6]([O-:7])=[O:5])[C:18]([C:19]([F:20])([F:21])[F:22])=[CH:17][N:16]=3)=[CH:29][CH:28]=2)[CH2:31][CH2:32]1)=[O:37])([CH3:42])([CH3:40])[CH3:41].[Li+:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68283092tert-Butyl 4-(4-((4-(3-(methoxycarbonyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Product 1

HCID 68282827Lithium 3-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzoateYield 91%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiOH.H2O (0.025 g, 0.60 mmol) was added to tert-butyl 4-(4-((4-(3-(methoxycarbonyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I33) (0.117 g, 0.200 mmol) in THF (7 mL), water (1.5 mL) and methanol (1 mL). The resulting mixture was allowed to stir at room temperature for 17 hours, the volatiles were removed in vacuo and the residue was diluted with EtOAc (100 mL) and sat. aq. NaHCO3 (80 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×80 mL), the organic layers were combined, washed with brine (70 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the title compound (I34) (0.105 g, 91% yield) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.00 (s, 1H), 8.60 (s, 1H), 7.85-7.74 (m, 2H), 7.56-7.48 (m, 2H), 7.47-7.35 (m, 2H), 6.93 (d, J=9.1 Hz, 2H), 3.50-3.41 (m, 4H), 3.17-2.98 (m, 8H), 1.42 (s, 9H). LCMS Method C: rt 6.30 min; m/z 572.3 [M+H]+.

Workup

  1. customthe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (100 mL) and sat. aq. NaHCO3 (80 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×80 mL)
  5. washwashed with brine (70 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4504941103aa40f09c719702df0a9efa
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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