MK 886 → 3-[1-(p-Chlorobenzyl)-3-(t-butylthio)-5-(i-propyl)-indole-2-yl]-2,2-dimethylpropanol

HRID 483418Notes

Reaction equation

HRID 483418 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]([CH3:18])[CH3:17])=[CH:13][CH:14]=3)[C:9]([S:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[C:8]2[CH2:24][C:25]([CH3:30])([CH3:29])[C:26](O)=[O:27])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]([CH3:18])[CH3:17])=[CH:13][CH:14]=3)[C:9]([S:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[C:8]2[CH2:24][C:25]([CH3:30])([CH3:29])[CH2:26][OH:27])=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 3651377MK 886HCID 21226445Aluminium lithium hydride

Product 1

HCID 150354093-[1-(p-Chlorobenzyl)-3-(t-butylthio)-5-(i-propyl)-indole-2-yl]-2,2-dimethylpropanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 200 mg of methyl 1-(p-chlorobenzyl)-3-(t-butylthio)-α,α-dimethyl-5-(i-propyl)-indole-2-propanoate (from Example 25) in 1.5 mL tetrahydrofuran (THF) was added 0.4 ml of a solution of lithium aluminum hydride (1.0 M in THF) at 0° C. After 2h at 0° C., the reaction mixture was quenched with saturated aqueous Na2SO4, diluted with ether and stirred at room temperature for 1 h. The resultant slurry was filtered and the filtrate concentrated to dryness. The resultant oil was purified by flash chromatography (eluant: hexane-ethyl acetate, 8:2) to give the title compound as a viscous oil. 1H NMR (250 MHz, Acetone D ) δ: 0.94 (s, 9H), 1.26 (s, 6H), 1.27 (d, 2H J=7.0 Hz), 2.95-3.08 (m, 2H), 2.99 (septuplet, 1H, J=7.0 Hz), 3.27 (d, 2H, J=7.0 Hz), 4.02 (t, 1H, J=7.0 Hz, exchanges with D20), 4.69 (broad s, 2H), 6.92 (d, 2H, J=8.5 Hz), 7.00 (dd, 1H, J=7.5 and 2.0 Hz), 7.24 (d, 1H, J=7.5 Hz); 7.29 (d, 2H, J=8.5 Hz), 7.58 (d, 1H, J=2.0 Hz) IR (CDCl3) 3420 cm-1.

Workup

  1. customAfter 2h at 0° C., the reaction mixture was quenched with saturated aqueous Na2SO4
  2. additiondiluted with ether
  3. filtrationThe resultant slurry was filtered
  4. concentrationthe filtrate concentrated to dryness
  5. customThe resultant oil was purified by flash chromatography (eluant: hexane-ethyl acetate, 8:2)

Sources & evidence

ORD record
ord-df5e1fa96d934720a49c8f361c42c2d6
Source dataset
uspto-grants-1993_07
Patent number
US05225421

Reaction notes

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