Pyrrolidine → HCID 13749161, compound

HRID 978713Notes

Reaction equation

HRID 978713 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]1[CH2:11][CH2:12][C:13]([CH3:17])([CH3:16])[CH:14](O)[C:6]1=[C:5]2[CH3:18].CS([Cl:23])(=O)=O.[NH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1>N1C=CC=CC=1>[ClH:23].[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]1[CH2:11][CH2:12][C:13]([CH3:17])([CH3:16])[CH:14]([N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[C:6]1=[C:5]2[CH3:18]

Participants

5

Reactant 3

HCID 31268Pyrrolidine2×HCID 31297Methanesulfonyl chlorideHCID 13749191HCID 13749191, compound

Product 1

HCID 13749161HCID 13749161, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-bromo-6,7,8,9-tetrahydro-8,8,10-trimethylpyrido[1,2-a]indol-9-ol (616 mg, 2 mmol) in anhydrous pyridine (10 mL) was added methanesulfonyl chloride (458 mg, 4 mmol) at room temperature. The reaction mixture was stirred for 60 minutes, cooled to 0° C., and distilled pyrrolidine (852 mg, 12 mmol) was added. Stirring was continued at room temperature for 2 hours, and then at 40° C. for 30 minutes. After adding a second portion of pyrrolidine (852 mg), the mixture was stirred at ambient temperature overnight, and then evaporated. The residue was partitioned between 5% aqueous NaHCO3 and ether. The organic layer was washed with 1.5% hydrochloric acid, and the separated aqueous part was basified (pH 8) with a saturated solution of NaHCO3. The product was extracted with ether, the combined extracts were dried (MgSO4), filtered, and evaporated. The residual oil was chromatographed on neutral alumina (activity III). Elution with chloroform-hexane 1:1 afforded 355 mg (63%) of the title base. The corresponding hydrochloride salt was crystallized from ethanol-ether, m.p. 183.5°-184.5° C.

Workup

  1. additionwas added
  2. stirringStirring
  3. waitwas continued at room temperature for 2 hours
  4. waitat 40° C. for 30 minutes
  5. stirringthe mixture was stirred at ambient temperature overnight
  6. customevaporated
  7. customThe residue was partitioned between 5% aqueous NaHCO3 and ether
  8. washThe organic layer was washed with 1.5% hydrochloric acid
  9. extractionThe product was extracted with ether
  10. dry with materialthe combined extracts were dried (MgSO4)
  11. filtrationfiltered
  12. customevaporated
  13. customThe residual oil was chromatographed on neutral alumina (activity III)
  14. washElution with chloroform-hexane 1:1

Sources & evidence

ORD record
ord-442510bab1944223a711d78eaa5c0679
Source dataset
uspto-grants-1987_05
Patent number
US04665183

Reaction notes

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