Sodium Sulfate → 4,6-difluoro-5-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-1H-indole-3-carboxylic acid

HRID 338285Notes

Reaction equation

HRID 338285 reaction equation
[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3([CH2:20][OH:21])[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([CH:23]=[O:24])=[CH:5][NH:6]2.Cl([O-])=[O:26].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>C(#N)C.C(O)(C)(C)C.CC(=CC)C.O>[F:1][C:2]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([C:17]3([CH2:20][OH:21])[CH2:18][CH2:19]3)=[CH:15][CH:16]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([C:23]([OH:26])=[O:24])=[CH:5][NH:6]2

Participants

8

Reactant 3

HCID 24436Sodium SulfateHCID 23668197Sodium ChloriteHCID 866986304,6-difluoro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde

Product 1

HCID 717662394,6-difluoro-5-(4-(1-(hydroxymethyl)cyclopropyl)phenyl)-1H-indole-3-carboxylic acidYield 24%

Reagents, catalysts & solvents 4

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

Procedure

To a solution of 4,6-difluoro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde (70 mg, 0.214 mmol) in acetonitrile (4.6 mL), t-Butanol (4.6 mL) and 2-methyl-2-butene (3.0 mL) was added a solution of sodium chlorite (289 mg, 4.28 mmol) and NaH2PO4 (590 mg, 4.28 mmol) in water (4.6 mL) at 0° C. The reaction mixture was stirred at room temperature for 18 h. The reaction was quenched with a solution of sodium sulfate (674 mg, 5.35 mmol) in water (5.0 mL), and extracted with ethyl acetate (20 mL×3). The organic layers were washed with brine (20 mL×1) and dried over sodium sulfate, filtered, concentrated, and purified which was purified by preparative HPLC to give the title compound (17.4 mg, 24%) as a white solid. MS (AP+) 343.9 (M+1)+. 1H NMR (400 MHz, CD3OD) δ 8.00 (s, 1H), 7.48 (d, 2H), 7.39 (d, 2H), 7.11 (d, 1H), 3.71 (s, 2H), 0.91 (s, 4H).

Workup

  1. extractionextracted with ethyl acetate (20 mL×3)
  2. washThe organic layers were washed with brine (20 mL×1)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-2dc4de3aa56a44e58bcc73898038ddab
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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