Lithium Hydroxide → 1-[4-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid

HRID 1028149Notes

Reaction equation

HRID 1028149 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:16]3[N:17]=[C:18]([N:21]4[CH2:26][CH2:25][CH:24]([C:27]([O:29]CC)=[O:28])[CH2:23][CH2:22]4)[S:19][CH:20]=3)[CH:13]=[CH:14][CH:15]=2)[N:4]=1.[OH-].[Li+]>O1CCCC1.CO.CC1CCCO1>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:16]3[N:17]=[C:18]([N:21]4[CH2:22][CH2:23][CH:24]([C:27]([OH:29])=[O:28])[CH2:25][CH2:26]4)[S:19][CH:20]=3)[CH:13]=[CH:14][CH:15]=2)[N:4]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 71075072Ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate

Product 1

HCID 683241951-[4-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acidYield 100%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 73012-MethyltetrahydrofuranSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate (38 mg, 0.08 mmol) in tetrahydrofuran (0.5 mL) and methanol (0.5 mL) was added 1M aqueous lithium hydroxide (0.5 mL, 0.5 mmol). The reaction was heated to 50° C. for 2 hours. The mixture was then cooled to room temperature, diluted with 2-methyltetrahydrofuran (30 mL), and washed with 0.1N aqueous hydrochloride acid (30 mL) and brine (30 mL). The aqueous fractions were further extracted with 2-methyltetrahydrofuran (30 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to provide 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid (36 mg, 0.08 mmol, quantitative) as a light blue solid. MS APCI: [M+H]+ m/z 450.1. 1H NMR (400 MHz, DMSO): δ 10.23 (s, 1H); 8.82 (d, J=4.9 Hz, 1H); 8.38 (s, 1H); 7.61 (d, J=7.8 Hz, 1H); 7.50 (d, J=7.8 Hz, 1H); 7.32 (t, J=7.8 Hz, 1H); 7.27 (d, J=5.0 Hz, 1H); 7.15 (s, 1H); 6.65 (s, 2H); 3.93 (d, J=12.3 Hz, 2H); 3.22-3.08 (m, 2H); 1.95 (d, J=13.1 Hz, 2H); 1.65 (d, J=14.4 Hz, 2H). rhSyk=++.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. washwashed with 0.1N aqueous hydrochloride acid (30 mL) and brine (30 mL)
  3. extractionThe aqueous fractions were further extracted with 2-methyltetrahydrofuran (30 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c9824ebb2c8744bcb980c1ebf76c9900
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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