Lithium hydroxide, monohydrate → 1-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxylic acid

HRID 592364ノート

反応式

HRID 592364 の反応式
C[O:2][C:3]([C:5]1([C:8]2[CH:45]=[CH:44][CH:43]=[CH:42][C:9]=2[CH2:10][CH2:11][C:12]2[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([CH:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]4)=[CH:25][CH:24]=3)[N:13]=2)[CH2:7][CH2:6]1)=[O:4].O[Li].O>C1COCC1.CO.O>[C:38]([O:37][C:35]([N:32]1[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[C:5]4([C:3]([OH:4])=[O:2])[CH2:6][CH2:7]4)[C:17]([C:18]([F:20])([F:19])[F:21])=[CH:16][N:15]=3)=[CH:28][CH:27]=2)[CH2:30][CH2:31]1)=[O:36])([CH3:41])([CH3:39])[CH3:40]

参加物

6

反応物 2

HCID 168937Lithium hydroxide, monohydrateHCID 86712285tert-Butyl 4-(4-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

生成物 1

HCID 867122861-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxylic acid収率 228.7%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
40 °C

実験手順

A solution of tert-butyl 4-(4-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A4) (0.304 g, 0.487 mmol) and LiOH.H2O (204 mg, 4.87 mmol) in THF (7 mL), MeOH (7 mL) and H2O (1.5 mL) was stirred at room temperature overnight. The resulting mixture was then heated to 40° C. and stirred for 3.5 days. The volatiles were removed under reduced pressure and the residue was taken up in EtOAc (50 mL). Aqueous HCl (2 M, 50 mL) was added cautiously and the layers were separated. The aqueous phase was extracted with EtOAc (2×50 mL), and then the combined organics were washed with brine and dried over MgSO4. The solvent was removed in vacuo to give the title compound A5 as a yellow oil (680 mg, 98%); LCMS-A: rt 6.793 min; m/z 609 [M−H]−.

後処理

  1. customThe volatiles were removed under reduced pressure
  2. additionAqueous HCl (2 M, 50 mL) was added cautiously
  3. customthe layers were separated
  4. extractionThe aqueous phase was extracted with EtOAc (2×50 mL)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed in vacuo

出典と根拠

ORDレコード
ord-ee4687652ac745f1a9f7f70314464e23
出典データセット
uspto-grants-2016_01
特許番号
US09238644B2

反応ノート

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