Acetic Anhydride → 2-Acetyl-5-methanesulfonamido-1,2,3,4-tetrahydroisoquinoline

HRID 2228484Notes

Reaction equation

HRID 2228484 reaction equation
Cl.[CH3:2][S:3]([NH:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH2:9][CH2:10][NH:11][CH2:12]2)(=[O:5])=[O:4].[C:17](OC(=O)C)(=[O:19])[CH3:18].C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.CO>[C:17]([N:11]1[CH2:10][CH2:9][C:8]2[C:13](=[CH:14][CH:15]=[CH:16][C:7]=2[NH:6][S:3]([CH3:2])(=[O:4])=[O:5])[CH2:12]1)(=[O:19])[CH3:18]

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 22218092N-(1,2,3,4-tetrahydroisoquinolin-5-yl)methanesulfonamide hydrochloride

Product 1

HCID 187684882-Acetyl-5-methanesulfonamido-1,2,3,4-tetrahydroisoquinolineYield 68%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-methanesulfonamido-1,2,3,4-tetrahydroisoquinoline hydrochloride (2.87 g, 0.011 mol) in dichloromethane at 0° C. was added acetic anhydride (1.2 ml, 0.013 mol) and triethylamine (3.4 ml, 0.024 mol), and the reaction was stirred at room temperature for 16 hours. The reaction mixture was then partitioned between ethyl acetate and aqueous sodium bicarbonate solution and the aqueous phase extracted with further portions of ethyl acetate. The combined organic extracts were dried (MgSO4) and evaporated to afford an oil. This was dissolved in methanol (15 ml) and treated with aqueous sodium carbonate solution (7%, w/w, 15 ml) and the mixture stirred for 16 hours at room temperature, after which time the methanol was removed under reduced pressure, the pH was adjusted to pH 8 with 2N hydrochloric acid and the product was extracted with ethyl acetate (2×). The combined organic extracts were dried (MgSO4) and evaporated to give an oil which was purified on silica gel, eluting with dichloromethane:methanol (95:5, v/v) to give the title compound as an oil (2.0 g, 68%). Rf 0.20 (dichloromethane:methanol 95:5, v/v). MS m/z 269 (MH)+.

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate and aqueous sodium bicarbonate solution
  2. extractionthe aqueous phase extracted with further portions of ethyl acetate
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. customevaporated
  5. customto afford an oil
  6. stirringthe mixture stirred for 16 hours at room temperature
  7. customafter which time the methanol was removed under reduced pressure
  8. extractionthe product was extracted with ethyl acetate (2×)
  9. dry with materialThe combined organic extracts were dried (MgSO4)
  10. customevaporated
  11. customto give an oil which
  12. customwas purified on silica gel
  13. washeluting with dichloromethane:methanol (95:5

Sources & evidence

ORD record
ord-e8297d75d5dd46ef89dcf7909f9abb5e
Source dataset
uspto-grants-2002_07
Patent number
US06417194B1

Reaction notes

Loading…