2-Methyl-2-butene → 5-{4-[1-(tert-butoxycarbonyl)pyrrolidin-2-yl]phenyl}-6-chloro-1H-indole-3-carboxylic acid

HRID 338424Notes

Reaction equation

HRID 338424 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][CH2:21][N:20]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:37].[Na+].P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].S([O-])([O-])=O.[Na+].[Na+]>C(#N)C.O.C(O)(C)(C)C>[C:27]([O:26][C:24]([N:20]1[CH2:21][CH2:22][CH2:23][CH:19]1[C:16]1[CH:17]=[CH:18][C:13]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[Cl:1])[NH:8][CH:7]=[C:6]3[C:11]([OH:37])=[O:12])=[CH:14][CH:15]=1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

9

Reactant 5

HCID 105532-Methyl-2-buteneHCID 24243Trisodium PhosphateHCID 24437Sodium SulfiteHCID 23668197Sodium ChloriteHCID 86698758tert-butyl 2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]pyrrolidine-1-carboxylate

Product 1

HCID 866987595-{4-[1-(tert-butoxycarbonyl)pyrrolidin-2-yl]phenyl}-6-chloro-1H-indole-3-carboxylic acidYield 84.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

The tert-butyl 2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]pyrrolidine-1-carboxylate (160 mg, 0.377 mmol) was dissolved in acetonitrile (9 mL) and warm t-butanol (9 mL) followed by the addition of 2-methyl-2-butene (6.00 mL, 56.5 mmol) and cooled to 0° C. followed by the addition of an aqueous solution of sodium chlorite (763 mg, 11.3 mmol) and sodium phosphate (monobasic and monohydrate, 1.56 g, 11.3 mmol) in water (5 mL) dropwise via additional funnel. The ice bath was removed and the mixture was allowed to warm to room temperature. The suspension was stirred overnight. To the suspension was added sodium sulfite (1.43 g, 11.3 mmol) in water (3 mL) and the resultant mixture concentrated to remove the organic solvent followed by extraction three times with ethyl acetate (15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to afford crude product which was purified by reverse phase HPLC to afford the title compound (140 mg, 84.2% yield).

Workup

  1. customThe ice bath was removed
  2. temperatureto warm to room temperature
  3. concentrationthe resultant mixture concentrated
  4. customto remove the organic solvent
  5. extractionfollowed by extraction three times with ethyl acetate (15 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford crude product which
  10. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-de000bc9adfa414b8c4288ee59b5a35a
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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