Lithium borohydride → (5-Benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methanol

HRID 404833Notes

Reaction equation

HRID 404833 reaction equation
[CH2:1]([C:8]1[S:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[C:21](OC)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C1SC(C2C=C(F)C=CC=2F)=NC=1C(OCC)=O)C1C=CC=CC=1.[Li+].[BH4-]>C1COCC1>[CH2:1]([C:8]1[S:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[CH2:21][OH:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 4148881Lithium borohydrideHCID 67451099Ethyl 5-benzyl-2-(2,5-difluorophenyl)thiazole-4-carboxylateHCID 67451131Methyl 5-benzyl-2-(2,5-difluorophenyl)thiazole-4-carboxylate

Product 1

HCID 67450892(5-Benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methanolYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of a mixture of methyl 5-benzyl-2-(2,5-difluorophenyl)thiazole-4-carboxylate and ethyl 5-benzyl-2-(2,5-difluorophenyl)thiazole-4-carboxylate (7.8 g, 21.70 mmol) in THF (72.3 mL) was slowly added LiBH4 (0.946 g, 43.4 mmol) at room temperature. The reaction mixture was stirred for overnight. After quenched with water, the reaction mixture was extracted with EtOAc. The organic layers was washed with saturated NaHCO3 solution and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by column chromatography to yield (5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methanol (6.66 g, 97%) as white solid. LC/MS (uplc): MH+ 318.2, 1.03 min.

Workup

  1. customat room temperature
  2. customAfter quenched with water
  3. extractionthe reaction mixture was extracted with EtOAc
  4. washThe organic layers was washed with saturated NaHCO3 solution and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-3c058fc8e22343a9b2da383496e68fce
Source dataset
uspto-grants-2014_06
Patent number
US08748626B2

Reaction notes

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