4-Hydroxypyrrolidine → 4-[(3-hydroxypyrrolidin-1-yl)methyl]-1-(phenylsulfonyl)-1H-indol-5-ol

HRID 2423117Notes

Reaction equation

HRID 2423117 reaction equation
C([O:8][C:9]1[CH:17]=[CH:16][C:15]2[N:14]([S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:13]=[CH:12][C:11]=2[C:10]=1[CH:27]=O)C1C=CC=CC=1.[OH:29][CH:30]1[CH2:34][CH2:33][NH:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])=O.[NH4+]>ClCCCl>[OH:29][CH:30]1[CH2:34][CH2:33][N:32]([CH2:27][C:10]2[C:9]([OH:8])=[CH:17][CH:16]=[C:15]3[C:11]=2[CH:12]=[CH:13][N:14]3[S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:19])=[O:20])[CH2:31]1

Participants

6

Reactant 4

HCID 982104-HydroxypyrrolidineHCID 2723923Ammonium formateHCID 5049666Sodium triacetoxyborohydrideHCID 866182505-(Benzyloxy)-1-(phenylsulfonyl)-1H-indole-4-carbaldehyde2×

Product 1

HCID 595135774-[(3-hydroxypyrrolidin-1-yl)methyl]-1-(phenylsulfonyl)-1H-indol-5-olYield 91.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 5-(benzyloxy)-1-(phenylsulfonyl)-1H-indole-4-carbaldehyde (Intermediate 4, 100 mg, 0.250 mmol) in DCE (3 mL) was added 3-hydroxypyrrolidine, (33 mg, 0.38 mmol) and sodium triacetoxyborohydride (0.16 g, 0.77 mmol) and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was dissolved in MeOH (2 mL) and Pd/C 10 wt. % (0.020 g, 0.019 mmol) was added and the mixture was flushed with N2 gas. Ammonium formate (0.050 g, 0.80 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was taken up in CHCl3/H2O, and the mixture was washed with water and brine, dried (MgSO4) and the solvent was removed under reduced pressure to give 4-[(3-hydroxypyrrolidin-1-yl)methyl]-1-(phenylsulfonyl)-1H-indol-5-ol (85 mg) as an oil. MS m/z 373 [M+H]+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in MeOH (2 mL)
  3. additionPd/C 10 wt. % (0.020 g, 0.019 mmol) was added
  4. customthe mixture was flushed with N2 gas
  5. stirringthe reaction mixture was stirred at room temperature overnight
  6. customThe solvent was removed under reduced pressure
  7. washthe mixture was washed with water and brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8526327283e149278e3c761af478b141
Source dataset
uspto-grants-2011_06
Patent number
US07960374B2

Reaction notes

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