2-Methyl-2-butene → HCID 86698614, compound

HRID 1054610Notes

Reaction equation

HRID 1054610 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][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]2)=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:37].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][CH:19]([C:16]2[CH:17]=[CH:18][C:13]([C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][C:2]=3[Cl:1])[NH:8][CH:7]=[C:6]4[C:11]([OH:37])=[O:12])=[CH:14][CH:15]=2)[CH2:20]1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium Chlorite2×HCID 23673460Sodium Phosphate, Monobasic, Dihydrate2×HCID 86698613HCID 86698613, compound

Product 1

HCID 86698614HCID 86698614, compoundYield 36.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 3-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]pyrrolidine-1-carboxylate (43 mg, 0.1 mmol) in acetonitrile (1.2 mL) and tert-butanol (1.2 mL) was added 2-methyl-2-butene (1.2 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (100 mg, 1.1 mmol) and sodium phosphate monobasic dihydrate (234 mg, 1.5 mmol) in water (0.6 mL). After the resulting mixture was stirred for 2 h at room temperature, additional sodium chlorite (134 mg, 1.47 mmol) and sodium phosphate monobasic dihydrate (312 mg, 2.0 mmol) in H2O (0.6 mL) was added to the reaction mixture. The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the aqueous residue was extracted with EtOAc (3×20 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in DMSO and purified via pre-HPLC to give 5-{4-[1-(tert-butoxycarbonyl)pyrrolidin-3-yl]phenyl}-6-chloro-1H-indole-3-carboxylic acid (16 mg, 36%) as a white solid. MS (ES+) 463.1 (M+Na)+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 16 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. extractionthe aqueous residue was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DMSO
  7. custompurified via pre-HPLC

Sources & evidence

ORD record
ord-24319a041da54a2bb87c8ac17bf191a3
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

Loading…