Aluminium lithium hydride → (S)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

HRID 42987Notes

Reaction equation

HRID 42987 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][C@H:9]([NH:14][S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[CH2:8]2)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:2][CH2:3][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][C@H:9]([NH:14][S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[CH2:8]2

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66733844(S)-methyl 2-(1-methylethylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 67088215(S)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideYield 103%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-methyl-2-(1-methylethylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (2.502 mmol, 744 mg) was dissolved in dry THF (20 mL) and was purged with nitrogen and cooled in an ice bath. Lithium aluminium hydride (7.51 mmol, 7.51 mL) was added dropwise and stirring continued at 0° C. for 10 min. The mixture was quenched by addition of methanol followed by 1:1 THF/water and 1N HCl before concentration to remove organics. The residue was partitioned between dichlormethane/1N HCl. and the phases mixed and separated. The aqueous layer was further extracted with DCM (×2) Combined organics washed with brine and concentrated before purification on silica eluting with 2% MeOH/DCM to give (S)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (0.692 g, 103%). 1H NMR (400 MHz, CDCl3) δ 1.39 (d, 6H) 1.71 (bt, 1H) 2.89 (m, 2H) 3.18 (sept, 1H) 3.30 (m, 2H) 4.28 (m, 1H) 4.41 (m, 1H) 4.66 (d, 2H) 7.18 (m, 2H) 7.24 (m, 1H)

Workup

  1. customwas purged with nitrogen
  2. temperaturecooled in an ice bath
  3. customThe mixture was quenched by addition of methanol
  4. concentrationfollowed by 1:1 THF/water and 1N HCl before concentration
  5. customto remove organics
  6. customThe residue was partitioned between dichlormethane/1N HCl
  7. additionand the phases mixed
  8. customseparated
  9. extractionThe aqueous layer was further extracted with DCM (×2)
  10. washCombined organics washed with brine
  11. concentrationconcentrated before purification on silica eluting with 2% MeOH/DCM

Sources & evidence

ORD record
ord-1ae2e28b171747fe8949f5c57582f6f8
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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