Aluminium lithium hydride → HCID 86591644, compound

HRID 2212971Notes

Reaction equation

HRID 2212971 reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=2)[NH:13][CH:12]=1)=[O:5].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=2)[NH:13][CH:12]=1)=[O:5]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86591643HCID 86591643, compound

Product 1

HCID 86591644HCID 86591644, compoundYield 70.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

Trans-2-(5-cyano-1H-indol-3-yl)-cyclopentanecarboxylic acid methoxy-methyl-amide (460 mg, 1.5 mMol) was dissolved in THF and cooled to −40° C. Lithium aluminum hydride (117 mg, 3.1 mMol) was added and the temperature was maintained between −40 and −30° C. for 1 h. The reaction was quenched with ethyl acetate (10 mL) and warmed to 0° C. The reaction was treated dropwise with water (0.12 mL) and stirred 5 min. Then sodium hydroxide (1N, 0.36 mL) was added and the reaction was stirred 5 min. Then a further addition of water (0.12 mL) was made and the reaction was stirred for 20 min. The reaction was filtered through celite and sand, and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel with ethyl acetate/hexanes (50%) to give the product as a clear oil (252 mg, 68%). 1H NMR (400 MHz, CDCl3) δ 9.67 (1H, d, J=2.8 Hz), 8.37 (1H, brs), 7.96 (1H, s), 7.36–7.44 (2H, m), 7.14 (1H, d, J=2.3 Hz), 3.60 (1H, q, J=8.5 Hz), 2.98 (1H, q of d, J=7.5, 2.7 Hz), 2.30 (1H, m), 1.71–2.20 (5H, m); MS m/e 239.2 (M+H).

Workup

  1. temperaturethe temperature was maintained between −40 and −30° C. for 1 h
  2. customThe reaction was quenched with ethyl acetate (10 mL)
  3. temperaturewarmed to 0° C
  4. additionThe reaction was treated dropwise with water (0.12 mL)
  5. additionThen sodium hydroxide (1N, 0.36 mL) was added
  6. stirringthe reaction was stirred 5 min
  7. additionThen a further addition of water (0.12 mL)
  8. stirringthe reaction was stirred for 20 min
  9. filtrationThe reaction was filtered through celite and sand
  10. customthe solvent was evaporated in vacuo
  11. customThe residue was purified by chromatography on silica gel with ethyl acetate/hexanes (50%)

Sources & evidence

ORD record
ord-de1b2ec74c744a3284ee3047cdff3ec8
Source dataset
uspto-grants-2006_09
Patent number
US07105516B2

Reaction notes

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