Water → 1-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclobutanecarboxylic acid

HRID 592453Notes

Reaction equation

HRID 592453 reaction equation
O[Li].O.C[O:5][C:6]([C:8]1([C:12]2[CH:49]=[CH:48][CH:47]=[CH:46][C:13]=2[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)[CH2:11][CH2:10][CH2:9]1)=[O:7].O.C(Cl)Cl>C1COCC1>[C:42]([O:41][C:39]([N:36]1[CH2:35][CH2:34][CH:33]([C:30]2[CH:29]=[CH:28][C:27]([NH:26][C:18]3[N:17]=[C:16]([CH2:15][CH2:14][C:13]4[CH:46]=[CH:47][CH:48]=[CH:49][C:12]=4[C:8]4([C:6]([OH:7])=[O:5])[CH2:11][CH2:10][CH2:9]4)[C:21]([C:22]([F:24])([F:23])[F:25])=[CH:20][N:19]=3)=[CH:32][CH:31]=2)[CH2:38][CH2:37]1)=[O:40])([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 4

HCID 962Water2×HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrate2×HCID 86712329tert-Butyl 4-(4-((4-(2-(1-(methoxycarbonyl)cyclobutyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 867123301-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclobutanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiOH.H2O (41 mg, 0.97 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(1-(methoxycarbonyl)cyclobutyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate A55 (31 mg, 0.049 mmol) in THF (5 mL) and H2O (0.5 mL) and the mixture was stirred at 40° C. overnight. Additional LiOH.H2O (400 mg, 9.53 mmol) was added and the mixture was heated at reflux for 12 days. Upon cooling DCM (50 mL) and water (50 mL) were added and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organics were dried (Na2SO4) and the volatiles were removed in vacuo to give the title compound A56 as a yellow oil (30 mg, 98%). LCMS-A: rt 7.586 min, m/z 625 [M+H]+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 12 days
  3. additionwere added
  4. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. customthe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-d5033bc91e874716b2e7924000438053
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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