Tetrahydrofuran → HCID 11646316, compound

HRID 1836614Notes

Reaction equation

HRID 1836614 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2[C@H:28]1[CH2:30][C@H:29]1C(=C)C(OC)=O)#[N:8].[O:37]1CCC[CH2:38]1>>[C:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)(=[O:19])=[O:20])[CH:13]=[C:12]2[C@H:28]1[CH2:30][C@H:29]1[CH2:38][OH:37])#[N:8]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 86587683HCID 86587683, compound

Product 1

HCID 11646316HCID 11646316, compoundYield 76%

Conditions

Temperature
-20 °C

Procedure

Powdered lithium aluminum hydride (120 mg, 3.16 mmol) was carefully added to a stirred solution of methyl [cis-2-[5-Cyano-1-(p-toluenesulfonyl)indol-3-yl]cycloprop-1-yl]-acrylate (185 mg, 0.47 mmol) in anhydrous tetrahydrofuran (10 ml) at −30° C. The resulting mixture was stirred at −20° C. for 1.5 h. The reaction was quenched with ethyl acetate (5 ml) and allowed to warmed to room temperature. After 10 min, water (120 μL) was added and after 5 min followed by a solution of aqueous sodium hydroxide (1N, 360 μL). After a further 5 min water (120 ml) was added and the solution was stirred 20 min. The aluminum salts were removed by vacuum filtration. The salts were rinsed with ethyl acetate (100 ml) and the combined filtrates were concentrated in vacuo. The crude material was purified by silica gel column chromatography with 45% ethyl acetate in hexanes to afford 131 mg (76% yield) of cis-2-[5-Cyano-1-(p-toluenesulfonyl)indol-3-yl]cyclopropanemethanol as a white solid : 1H NMR (400 MHz, CDCl3): δ8.04 (1H, d, J=8.6 Hz), 7.99 (1H, d, J=1.0 Hz), 7.74 (2H, d, J=6.8 Hz), 7.57 (1H, dd, J=8.6, 1.6 Hz), 7.44 (1H, d, J=1.3 Hz), 7.26 (2H, d, J=8.2 Hz), 3.50 (1H, m), 3.16 (1H, m), 2.36 (3H, s), 2.05 (1H, m), 1.60 (1H, m), 1.19 (1H, m), 0.99 (1H, t, J=5.5 Hz), 0.72 (1H, q, J=5.6 Hz); MS m/e 349 (M−OH)−.

Workup

  1. customThe reaction was quenched with ethyl acetate (5 ml)
  2. temperatureallowed to warmed to room temperature
  3. waitAfter 10 min
  4. additionwater (120 μL) was added and after 5 min
  5. additionAfter a further 5 min water (120 ml) was added
  6. stirringthe solution was stirred 20 min
  7. customThe aluminum salts were removed by vacuum filtration
  8. washThe salts were rinsed with ethyl acetate (100 ml)
  9. concentrationthe combined filtrates were concentrated in vacuo
  10. customThe crude material was purified by silica gel column chromatography with 45% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0f91017a74824eb4a442c19ef26e6bb8
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Reaction notes

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