Methanesulfonic Acid → HCID 89669848, compound

HRID 1775246Notes

Reaction equation

HRID 1775246 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:22]([O:24][CH3:25])=[O:23])[C:5]2[CH:6]=[C:7]([C@@:11]3([CH3:21])[CH2:15][CH2:14][CH2:13][N:12]3[CH2:16][C:17](OC)=[O:18])[NH:8][C:9]=2[CH:10]=1.CS(O)(=O)=O.C([O-])(O)=O.[Na+]>O>[F:1][C:2]1[CH:3]=[C:4]([C:22]([O:24][CH3:25])=[O:23])[C:5]2[C:6]3[C:17](=[O:18])[CH2:16][N:12]4[C@:11]([CH3:21])([CH2:15][CH2:14][CH2:13]4)[C:7]=3[NH:8][C:9]=2[CH:10]=1

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 516892Sodium BicarbonateHCID 89657458HCID 89657458, compound

Product 1

HCID 89669848HCID 89669848, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

In a 25-mL flask, (R)-methyl 6-fluoro-2-(1-(2-methoxy-2-oxoethyl)-2-methylpyrrolidin-2-yl)-1H-indole-4-carboxylate (100 mg) was treated with anhydrous MeSO3H (6 mL). The flask was fitted with a reflux condenser and heated at 60° C. for 1 h. Then, the reaction mixture was cooled in an ice-bath and diluted with distilled water (6.0 mL). The pH of the solution was increased to pH ˜10 by the addition of saturated aq. NaHCO3. The reaction mixture was then extracted with EtOAc (3×5 mL). The organic extracts were combined and washed with brine (1×5 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by Pre-TLC to give (R)-methyl 9-fluoro-11b-methyl-6-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-7-carboxylate (30 mg). 1H NMR (CDCl3-d) δ 7.14-7.224 (m, 2H), 4.03 (s, 3H), 3.81-3.84 (m, 1H), 3.57-3.59 (m, 1H), 3.22-3.24 (m, 1H), 2.92-2.94 (m, 1H), 2.39-2.40 (m, 1H), 2.16-2.17 (m, 1H), 1.93-1.94 (m, 1H), 1.63 (s, 3H), and 1.56-1.57 (m, 1H). MS (ESI) m/e [M+1]+ 317.0.

Workup

  1. customThe flask was fitted with a reflux condenser
  2. temperatureThen, the reaction mixture was cooled in an ice-bath
  3. extractionThe reaction mixture was then extracted with EtOAc (3×5 mL)
  4. washwashed with brine (1×5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Pre-TLC

Sources & evidence

ORD record
ord-50695b38ca1f4a9981c26874adfefdc7
Source dataset
uspto-grants-2016_02
Patent number
US09260440B2

Reaction notes

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