Aluminium lithium hydride → 4-[2-Hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 550842Notes

Reaction equation

HRID 550842 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]([C:25](OCC)=[O:26])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=2)[CH2:25][OH:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 671519624-[Ethoxycarbonyl-(3-trifluoromethyl-phenyl)-methyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 590119734-[2-Hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-piperazine-1-carboxylic acid tert-butyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-[Ethoxycarbonyl-(3-trifluoromethyl-phenyl)-methyl]-piperazine-1-carboxylic acid tert-butyl ester (2.10 g, 5.05 mmol) in tetrahydrofuran (30 mL) at 0° C. was added lithium aluminum hydride (1M in tetrahydrofuran, 7.57 mL, 7.57 mmol) dropwise. The mixture was stirred at 0° C. for two hours. The excess LAH was quenched with ethyl acetate and the mixture was stirred with sodium sulfate decahydrate for 10 minutes. The slurry was filtered and the filtrate partitioned between ethyl acetate and water. The organic layer was dried with magnesium sulfate. Filtration, concentration gave a crude which was loaded onto a column of silica gel. Elution with 40% ethyl acetate/hexanes gave 4-[2-Hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester (1.4 g, 74% yield) as a colorless oil. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. customThe excess LAH was quenched with ethyl acetate
  2. stirringthe mixture was stirred with sodium sulfate decahydrate for 10 minutes
  3. filtrationThe slurry was filtered
  4. customthe filtrate partitioned between ethyl acetate and water
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationFiltration, concentration
  7. customgave a crude which
  8. washElution with 40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-24034ec217a94d14aacaea9678800e8f
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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