Aluminium lithium hydride → N-(1-(3-(4-Chlorophenyl)-1-hydroxypentan-3-yl)-1H-indol-4-yl)methanesulfonamide

HRID 1477917Notes

Reaction equation

HRID 1477917 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:16]2[C:24]3[C:19](=[C:20]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17]2)([CH2:14][CH3:15])[CH2:9][C:10](OC)=[O:11])=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:16]2[C:24]3[C:19](=[C:20]([NH:25][S:26]([CH3:29])(=[O:27])=[O:28])[CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17]2)([CH2:14][CH3:15])[CH2:9][CH2:10][OH:11])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 70564698Methyl 3-(4-chlorophenyl)-3-(4-(methylsulfonamido)-1H-indol-1-yl)pentanoate

Product 1

HCID 70560533N-(1-(3-(4-Chlorophenyl)-1-hydroxypentan-3-yl)-1H-indol-4-yl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the product of Step H (60 mg, 0.138 mmol) in THF (5 mL) was added LiAlH4 (10.4 mg, 0.276 mmol) at 0° C. The mixture was stirred for 1 h and quenched with H2O (2 mL), extracted with ethyl acetate, and washed with brine (5 mL), dried over sodium sulfate, then filtered. After removing the organic solvent, the residue was purified by silica gel chromatography (EA/PE=1:3) to afford the title racemic compound. The racemic compound was submitted to chiral SFC separation using AS-H column (50% EtOH/CO2, 4.6×250 mm, 39.3° C.) to give two separated enantiomers. LC/MS m/z=406.9[M+H]+.

Workup

  1. customquenched with H2O (2 mL)
  2. extractionextracted with ethyl acetate
  3. washwashed with brine (5 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customAfter removing the organic solvent
  7. customthe residue was purified by silica gel chromatography (EA/PE=1:3)
  8. customto afford the title racemic compound
  9. customThe racemic compound was submitted to chiral SFC separation
  10. customAS-H column (50% EtOH/CO2, 4.6×250 mm, 39.3° C.)
  11. customto give two separated enantiomers

Sources & evidence

ORD record
ord-17f62b30eb5b44c5857f684508449bca
Source dataset
uspto-grants-2016_08
Patent number
US09403807B2

Reaction notes

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