Diisobutylaluminum hydride → 2-(4-((2-(3-Chlorophenyl)-6-ethylpyrimidin-4-yl)amino)phenyl)-3,3,3-trifluoropropan-1-ol

HRID 1508876Notes

Reaction equation

HRID 1508876 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH:21]([C:27]([F:30])([F:29])[F:28])[C:22](OCC)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH2:31][CH3:32])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CC(C[AlH]CC(C)C)C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([CH:21]([C:27]([F:28])([F:29])[F:30])[CH2:22][OH:23])=[CH:19][CH:20]=3)[CH:11]=[C:10]([CH2:31][CH3:32])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 90112388Ethyl 2-(4-((2-(3-chlorophenyl)-6-ethylpyrimidin-4-yl)amino)phenyl)-3,3,3-trifluoropropanoate

Product 1

HCID 1180371552-(4-((2-(3-Chlorophenyl)-6-ethylpyrimidin-4-yl)amino)phenyl)-3,3,3-trifluoropropan-1-olYield 55.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl 2-(4-((2-(3-chlorophenyl)-6-ethylpyrimidin-4-yl)amino)phenyl)-3,3,3-trifluoropropanoate (0.070 g, 0.15 mmol) in dichloromethane (3 mL) at 0° C. was slowly treated with DIBAL (0.064 g, 0.45 mmol) dropwise and the resulting mixture was stirred for 2 h and then warmed to rt for 2 h. After this time, the reaction was quenched with methanol, 2M HCl, and water and then extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (0.035 g, 51%) as a white solid. MW=421.84. 1H NMR (DMSO-d6, 300 MHz) δ 9.71 (s, 1H), 8.38-8.27 (m, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.61-7.52 (m, 2H), 7.39 (d, J=8.4 Hz, 2H), 6.63 (s, 1H), 5.10 (t, J=5.4 Hz, 1H), 4.02-3.91 (m, 1H), 3.90-3.80 (m, 1H), 3.77-3.61 (m, 1H), 2.69 (q, J=7.6 Hz, 2H), 1.27 (t, J=7.6 Hz, 3H); APCI MS m/z 422 [M+H]+.

Workup

  1. customAfter this time, the reaction was quenched with methanol, 2M HCl, and water
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was purified by column chromatography (silica, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d74f96b29eff43e48c59511362937163
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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