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

HRID 42983Notes

Reaction equation

HRID 42983 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 67025663(R)-methyl-2-(1-methylethylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 67025426(R)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-methyl-2-(1-methylethylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (7.13 mmol, 2.12 g) was dissolved in dry THF (100 mL) and the vessel purged with nitrogen. Lithium aluminium hydride (1M, 14.3 mmol, 14.3 mL) was added dropwise and stirring continued for 20 min. The mixture was quenched by addition of methanol followed by water and 1N HCl before concentration to remove organics. The residue was partitioned between EtOAc/1N HCl. and the phases mixed and separated. The aqueous layer was further extracted with EtOAc (×2) Combined organics washed with brine and concentrated before purification on silica eluting with 1% MeOH/DCM to give (R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide as a light coloured solid (1.76 g, 92%). 1H NMR (400 MHz, CDCl3) δ 1.40 (d, 6H) 1.60 (bs, 1H) 2.90 (m, 2H) 3.18 (sept, 1H) 3.32 (m, 2H) 4.19-4.33 (m, 2H) 4.66 (s, 2H) 7.20 (m, 2H) 7.26 (m, 1H)

Workup

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

Sources & evidence

ORD record
ord-ee2b6d07131a4c10abc2aca39087f9fc
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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