Diisobutylaluminum hydride → HCID 86732039, compound

HRID 1498781Notes

Reaction equation

HRID 1498781 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[C:13]([N:15]2[C:19]([CH3:20])=[N:18][C:17]([CH3:21])=[N:16]2)[N:12]=[C:11]([C:22]([F:25])([F:24])[F:23])[N:10]=1)=O)C.CC(C[AlH]CC(C)C)C>C1COCC1>[CH3:21][C:17]1[N:18]=[C:19]([CH3:20])[N:15]([C:13]2[N:12]=[C:11]([C:22]([F:25])([F:24])[F:23])[N:10]=[C:9]([C@@H:7]3[CH2:8][C@H:6]3[CH2:4][OH:3])[CH:14]=2)[N:16]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 86732040HCID 86732040, compound

Product 1

HCID 86732039HCID 86732039, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of ethyl-trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl)cyclopropanecarboxylate (16-4, 430 mg, 1.21 mmol, 1.0 eq.) in anhydrous THF (13.0 mL) at 0° C. was added DIBAL-H (1.0 M in toluene, 3.63 mL, 3.63 mmol, 3.0 eq.) dropwise. The resulting mixture was stirred at 0° C. for 2 hours under an atmosphere of nitrogen gas. The mixture was then quenched with saturated aqueous Rochelle's salt solution (10 mL) at 0° C. and vigorously stirred at room temperature for 1 hour. After dilution with H2O (50 mL), the biphasic mixture was separated. The separated aqueous layer was extracted with EtOAc (3×50 mL). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated to dryness to give trans-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl)cyclopropyl)methanol (16-5) as an off-white solid which was carried forward for next step without further purification. 1H NMR (300 MHz, CDCl3) δ 7.87 (s, 1H), 3.86-3.75 (m, 1H), 3.67-3.56 (m, 1H), 2.91 (s, 3H), 2.42 (s, 3H), 2.15 (m, 1H), 2.09-1.97 (m, 1H), 1.63-1.49 (m, 2H). LRMS m/z (M+H) 314 found, 314 required.

Workup

  1. customThe mixture was then quenched with saturated aqueous Rochelle's salt solution (10 mL) at 0° C.
  2. stirringvigorously stirred at room temperature for 1 hour
  3. customAfter dilution with H2O (50 mL), the biphasic mixture was separated
  4. extractionThe separated aqueous layer was extracted with EtOAc (3×50 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-910361ef1d9f4d70af827e2a2f3f47d8
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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