Sodium Sulfite → 5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-6-methyl-1H-indole-3-carboxylic acid

HRID 338296Notes

Reaction equation

HRID 338296 reaction equation
[OH:1][CH2:2][C:3]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][C:20]=3[CH3:21])[NH:17][CH:16]=[C:15]4[CH:22]=[O:23])=[CH:8][CH:7]=2)[CH2:5][CH2:4]1.Cl([O-])=[O:25].[Na+].P([O-])(O)(O)=O.[Na+].S([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C(O)(C)(C)C.CC(=CC)C.O>[OH:1][CH2:2][C:3]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][C:20]=3[CH3:21])[NH:17][CH:16]=[C:15]4[C:22]([OH:25])=[O:23])=[CH:10][CH:11]=2)[CH2:4][CH2:5]1

Participants

9

Reactant 4

HCID 24437Sodium SulfiteHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 866986415-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-6-methyl-1H-indole-3-carbaldehyde

Product 1

HCID 866986425-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-6-methyl-1H-indole-3-carboxylic acidYield 18%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 105532-Methyl-2-buteneSolvent

Procedure

To a solution of 5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-6-methyl-1H-indole-3-carbaldehyde (50 mg, 0.164 mmol) in acetonitrile (3.3 mL), t-butanol (3.3 mL) and 2-methyl-2-butene (2.2 mL) was added a solution of sodium chlorite (221 mg, 3.28 mmol) and sodium dihydrogen phosphate (452 mg, 3.28 mol) in water (3.3 mL) at 0° C. The reaction mixture was stirred at room temperature for 18 h. TLC (petroleum ether/EtOAc=1:1) showed most of the starting material was consumed. The reaction was quenched with a solution of sodium sulfite (455 mg, 3.61 mmol) in water (3.0 mL), and extracted with ethyl acetate (20 mL×3). The organic layers were washed with brine (20 mL) and dried over sodium sulfate, filtered and concentrated to give a crude residue, which was purified by reverse phase HPLC to give the title compound (9.3 mg, 18%) as a white solid. MS (AP+) 322.1 (M+1)+. 1H NMR (400 MHz, CD3OD) 7.89 (s, 1H), 7.82 (s, 1H), 7.40 (d, 2H), 7.30 (s, 1H), 7.28 (d, 2H), 3.69 (s, 2H), 2.30 (s, 3H), 0.89 (m, 4H).

Workup

  1. customwas consumed
  2. extractionextracted with ethyl acetate (20 mL×3)
  3. washThe organic layers were washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude residue, which
  8. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-93405f9e14af4e49be1b49085fb7a5fe
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

Loading…