Indoline → HCID 68902902, compound

HRID 2110361Notes

Reaction equation

HRID 2110361 reaction equation
[F:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[CH:6][CH:7]=1.C(=O)(O)[O-].[Na+].[OH:27]OS([O-])=O.[K+].[NH:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35][CH2:34]1>ClCCl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.[O-2].[O-2].[Mn+4].CC(C)=O>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:10]1[C@H:9]([OH:27])[C@@H:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[N:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

9

Reactant 4

HCID 10328IndolineHCID 516892Sodium BicarbonateHCID 23707502Potassium hydroxy sulfiteHCID 86600901HCID 86600901, compound

Product 1

HCID 68902902HCID 68902902, compoundYield 9.8%

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 178418406HCID 178418406, compoundCatalystHCID 180AcetoneSolventHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
90 °C

Procedure

tert-Butyl (2S)-2-[(E)-2-(3-fluorophenyl)vinyl]pyrrolidine-1-carboxylate (400 mg, 1.37 mmol) was dissolved in dichloromethane (50 mL). A saturated aqueous solution of sodium bicarbonate (50 mL) was added, followed by acetone (10 mL) and tetrabutylammonium hydrogen sulfate (46 mg, 0.14 mmol). With vigorous stirring Oxone (8.4 g, 13.7 mmol) was added over 2 hours in 8 portions (1.05 g every 15 minutes). The mixture was stirred an additional 16 hours then diluted with dichloromethane. The organic layer was separated and washed with water, and saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified via Isco chromatography (Redisep, silica, 20% ethyl acetate/hexane) to give 240 mg that was immediately combined with indoline (0.14 g, 1.2 mmol) and heated to 90° C. for 16 hours. The mixture was cooled and the crude orange oil was purified by Isco chromatography (Redisep, silica, gradient 0% to 25% ethyl acetate in hexane) to give 130 mg that was immediately dissolved in dichloromethane (20 mL). Manganese dioxide (0.86 g, 10 mmol) was added and the mixture was stirred for 5 hours, then diluted with dichloromethane and filtered through a pad of Celite and concentrated. The crude product was purified by Isco chromatography (Redisep, silica, gradient 0% to 50% ethyl acetate in hexane) to give 50 mg of (S)-2-[2-(R)-(3-fluoro-phenyl)-1-hydroxy-2-indol-1-yl-ethyl]-(S)-pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. additionwas added over 2 hours in 8 portions (1.05 g every 15 minutes)
  2. customThe organic layer was separated
  3. washwashed with water, and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified via Isco chromatography (Redisep, silica, 20% ethyl acetate/hexane)
  8. customto give 240 mg that
  9. temperatureThe mixture was cooled
  10. customthe crude orange oil was purified by Isco chromatography (Redisep, silica, gradient 0% to 25% ethyl acetate in hexane)
  11. customto give 130 mg that
  12. stirringthe mixture was stirred for 5 hours
  13. filtrationfiltered through a pad of Celite
  14. concentrationconcentrated
  15. customThe crude product was purified by Isco chromatography (Redisep, silica, gradient 0% to 50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-95c002692e9e4fe5aabe32815f2931b8
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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