Sodium methanesulfinate → HCID 68153568, compound

HRID 1405368Notes

Reaction equation

HRID 1405368 reaction equation
[CH3:1][S:2]([O-:4])=[O:3].[Na+].Br[C:7]1[N:11]2[CH2:12][CH2:13][N:14]([CH3:31])[C:15]3([CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:22])[CH2:17][CH2:16]3)[C:10]2=[CH:9][CH:8]=1>[Cu]I.CS(C)=O>[CH3:31][N:14]1[C:15]2([CH2:16][CH2:17][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:19][CH2:20]2)[C:10]2=[CH:9][CH:8]=[C:7]([S:2]([CH3:1])(=[O:4])=[O:3])[N:11]2[CH2:12][CH2:13]1

Participants

5

Reactant 2

HCID 2733271Sodium methanesulfinateHCID 68153680HCID 68153680, compound

Product 1

HCID 68153568HCID 68153568, compoundYield 52.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of sodium methanesulfinate (293 mg, 2.87 mmol), benzyl 6-bromo-2-methyl-spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (1.00 g, 2.39 mmol), CuI (296 mg, 1.55 mmol) and DMSO (5 mL) was heated at 90° C. in a pressure vessel for 20 hours. The mixture was cooled and was partitioned between ether (10 mL) and water (10 mL). The organic layer was separated and the aqueous layer was extracted with ether (3×5 mL). The combined organic layers were washed with brine (2×10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography utilizing a gradient of 0-50% ethyl acetate in CH2Cl2 to yield benzyl 2-methyl-6-methylsulfonyl-spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (520 mg, 52%) as a white solid. ESI-MS m/z calc. 417.2, found 418.3 (M+1)+; Retention time: 1.27 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.45-7.30 (m, 5H), 6.88 (d, J=4.1 Hz, 1H), 6.01 (d, J=3.9 Hz, 1H), 5.15 (s, 2H), 4.28-4.15 (m, 2H), 4.09-3.89 (m, 2H), 3.40-3.16 (m, 4H), 3.10 (s, 3H), 2.37 (s, 3H), 2.20-2.02 (m, 2H), 1.89-1.66 (m, 2H).

Workup

  1. temperatureThe mixture was cooled
  2. customwas partitioned between ether (10 mL) and water (10 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ether (3×5 mL)
  5. washThe combined organic layers were washed with brine (2×10 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-c17309806c2046788526342f7dd1c192
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

Loading…