Aluminium lithium hydride → HCID 44555548, compound

HRID 42985Notes

Reaction equation

HRID 42985 reaction equation
C([O:3][C:4]([C:6]1[C:7]([C:28]([F:31])([F:30])[F:29])=[N:8][N:9]([CH2:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[CH2:17][C@@H:16]([NH:21][S:22]([CH:25]([CH3:27])[CH3:26])(=[O:24])=[O:23])[CH2:15]3)[CH:10]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:3][CH2:4][C:6]1[C:7]([C:28]([F:29])([F:31])[F:30])=[N:8][N:9]([CH2:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[CH2:17][C@@H:16]([NH:21][S:22]([CH:25]([CH3:27])[CH3:26])(=[O:24])=[O:23])[CH2:15]3)[CH:10]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 67088231(R)-ethyl 1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 44555548HCID 44555548, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-ethyl-1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.416 mmol, 1.11 g) was dissolved in THF (20 mL) and the vessel purged with nitrogen. Lithium aluminium hydride (1M, 4.83 mmol, 4.83 mL) was added dropwise and the mixture stirred at room temperature for 1 h. The reaction was quenched by addition of MeOH followed by water before concentration. The residue was partitioned between 1N HCl and EtOAc and the organic phase collected. The aqueous phase was further extracted with EtOAc (×2). Combined organics were dried and concentrated before purification on silica eluting with 30% EtOAc/iso-hexane followed by 50% EtOAc/iso-hexane. Desired fractions were collected and concentrated to give (R)—N-(5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1 H-inden-2-yl)propane-2-sulfonamide as a colourless glass (0.690 g, 68.5%). MS (ESI): m/z [M+Na]+ 440.5

Workup

  1. customthe vessel purged with nitrogen
  2. customThe reaction was quenched by addition of MeOH
  3. concentrationfollowed by water before concentration
  4. customThe residue was partitioned between 1N HCl and EtOAc
  5. customthe organic phase collected
  6. extractionThe aqueous phase was further extracted with EtOAc (×2)
  7. customCombined organics were dried
  8. concentrationconcentrated before purification on silica eluting with 30% EtOAc/iso-hexane
  9. customDesired fractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-2de17111c7b54057852a4959e0ea95a1
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

Loading…