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

HRID 1473108Notes

Reaction equation

HRID 1473108 reaction equation
C[O:2][C:3](=[O:43])[CH2:4][C:5]1[CH:42]=[CH:41][CH:40]=[CH:39][C:6]=1[CH2:7][CH2:8][C:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][N:12]=[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]3[O:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]3)=[CH:22][CH:21]=2)[N:10]=1.O.[OH-].[Li+]>C1COCC1.O>[C:35]([O:34][C:32]([N:28]1[CH2:29][CH2:30][O:31][CH:26]([C:23]2[CH:24]=[CH:25][C:20]([NH:19][C:11]3[N:10]=[C:9]([CH2:8][CH2:7][C:6]4[CH:39]=[CH:40][CH:41]=[CH:42][C:5]=4[CH2:4][C:3]([OH:43])=[O:2])[C:14]([C:15]([F:16])([F:17])[F:18])=[CH:13][N:12]=3)=[CH:21][CH:22]=2)[CH2:27]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71229333HCID 71229333, compound

Product 1

HCID 682828512-(2-(2-(2-((4-(4-(tert-Butoxycarbonyl)morpholin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acidYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 2-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)morpholine-4-carboxylate (I89) (46 mg, 0.077 mmol) was dissolved in THF (2 mL), and lithium hydroxide hydrate (6.0 mg, 0.15 mmol) in water (0.5 mL) was added. After 18 hours the mixture was concentrated, diluted with water (5 mL) and the pH adjusted to 3 with 6 M HCl. The mixture was extracted with ethyl acetate (3×10 mL), and the combined organic extracts washed with brine (20 mL), dried over sodium sulfate and evaporated to give the title compound (I90) (39 mg, 85% yield) as a pale yellow syrup; 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.54 (d, J=8.4 Hz, 2H), 7.35-7.27 (m, 4H), 4.38 (d, J=10.1 Hz, 1H), 4.07-3.80 (m, 5H), 3.67 (td, J=11.7, 2.7 Hz, 1H), 3.06 (s, 4H), 2.84 (s, 2H), 1.47 (s, 9H). LCMS Method C: rt 6.49 min; m/z 587.1 [M+H]+, 531.0 [M−tBu+2H]+, 487.1 [M-Boc+2H]+; m/z 585.2 [M−H]+.

Workup

  1. concentrationAfter 18 hours the mixture was concentrated
  2. additiondiluted with water (5 mL)
  3. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
  4. washthe combined organic extracts washed with brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. customevaporated

Sources & evidence

ORD record
ord-0e0ba08a929149438c514cb68cfae6f8
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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