Sulfolane → methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate

HRID 42505Notes

Reaction equation

HRID 42505 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH:14]=O)=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.C1(C)C=CC(S(=O)=O)=CC=1.S1(CCCC1)(=O)=O.C([BH3-])#N.[Na+]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=2[CH:10]=1

Participants

7

Reactant 4

HCID 31347SulfolaneHCID 5003444Sodium cyanoborohydrideHCID 86677357methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylateHCID 178427284HCID 178427284, compound

Product 1

HCID 67464634methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylateYield 89.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylate (60 g, 185 mmol) in DMF (220 mL) was added p-toluenesulfonic acid mono hydride (4.57 g, 24 mmol), p-toluenesulfonyl hydrazide (44.8 g, 240 mmol) followed by sulfolane (220 mL). The mixture was stirred at 100° C. for 1 h. The contents were cooled to room temperature and then sodium cyanoborohydride (46.5 g, 740 mmol) was added portion wise over a period of 25 min. Then the mixture was stirred at 100° C. for 2 h. Then the reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with water and extracted with 20% EtOAc: Pet ether, finally organic layer was washed with cold water, brine solution dried over anhydrous Na2SO4 and concentrated. Crude compound was purified by column chromatography using silica gel (100-200 mesh) and 20% DCM: Pet ether as an eluent to afford desired product methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate (24 g, 89.2% purity), (16 g, and 62.2% purity). 1H NMR (CDCl3, 400 MHz) δ 1.486 (d, J=6.4 Hz, 6H), 2.361 (s, 3H), 3.947 (s, 3H), 4.535-4.602 (m, 1H), 7.080 (s, 1H), 7.619 (s, 1H), 7.684 (s, 1H). LCMS (ES+) m/z=310.07 (M+H)

Workup

  1. temperatureThe contents were cooled to room temperature
  2. stirringThen the mixture was stirred at 100° C. for 2 h
  3. stirringThen the reaction mixture was stirred for 16 h at room temperature
  4. extractionextracted with 20% EtOAc
  5. washPet ether, finally organic layer was washed with cold water, brine solution
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customCrude compound was purified by column chromatography

Sources & evidence

ORD record
ord-e9d49779bb894004b06fed95826ce42e
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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