Diisobutylaluminum hydride → [2-(4-Fluorophenyl)-1,3-thiazol-4-yl]methanol

HRID 875024Notes

Reaction equation

HRID 875024 reaction equation
CC(C[AlH]CC(C)C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[S:18][CH:19]=[C:20]([C:22](OC)=[O:23])[N:21]=2)=[CH:13][CH:12]=1>C1COCC1>[F:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[S:18][CH:19]=[C:20]([CH2:22][OH:23])[N:21]=2)=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 67325329Methyl 2-(4-fluorophenyl)-1,3-thiazole-4-carboxylate

Product 1

HCID 39242197[2-(4-Fluorophenyl)-1,3-thiazol-4-yl]methanolYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIBAL-H (2.48 mL, 2.98 mmol, 1.2M in toluene) was added dropwise to a solution of methyl 2-(4-fluorophenyl)thiazole-4-carboxylate (300 mg, 1.26 mmol) in dry THF (6 mL) at −30° C. The reaction mixture was allowed to warm up to room temperature and stirred for 10 h. The reaction mixture was quenched carefully with saturated NH4Cl solution, filtered through Celite and diluted with EtOAc. The organic layer was separated, washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 25% EtOAc in petroleum ether) to afford (2-(4-fluorophenyl)thiazol-4-yl)methanol (130 mg, yield 54%). 1H NMR (300 MHz, CDCl3) δ 7.96-7.91 (dd, J=9.0 Hz, 5.3 Hz, 2H), 7.18-7.11 (m, 3H), 4.84-4.82 (d, J=5.3 Hz, 2H), 2.38-2.34 (t, J=6.2 Hz, 1H). MS (ESI) m/z: Calculated for C10H8FNOS: 209.03. found: 209.9 (M+H)+

Workup

  1. customThe reaction mixture was quenched carefully with saturated NH4Cl solution
  2. filtrationfiltered through Celite
  3. additiondiluted with EtOAc
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 25% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-fd5637869dc04b88a94259c8be0e31c1
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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