Methanesulfonic Acid → HCID 23128313, compound

HRID 1971651Notes

Reaction equation

HRID 1971651 reaction equation
CS(O)(=O)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[CH2:20]([O:22][C:23](=[O:37])[C:24]([NH:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1)=O)[CH3:21].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[CH3:36][O:35][C:31]1[CH:30]=[C:29]2[C:34](=[CH:33][CH:32]=1)[C:24]([C:23]([O:22][CH2:20][CH3:21])=[O:37])=[N:26][CH2:27][CH2:28]2

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 11430Potassium CarbonateHCID 14812Phosphorus oxide (P4O10)HCID 28710182HCID 28710182, compound2×

Product 1

HCID 23128313HCID 23128313, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 160 ml of methanesulfonic acid and 45 g of P2O5 was heated with stirring at an oil bath for about ½ hr in order to obtain a homogeneous mixture. The mixture was cooled to RT and a solution of 46 g of N-[2-(3-methoxyphenyl)-ethyl]oxalamic acid ethylester, 5b, in 50 ml of CH2Cl2 was added and the temperature was raised again to 80° C., while distilling off the CH2Cl2. The mixture was kept for 16 hr at 80° C. in order to complete the cyclization reaction. Then the reaction mixture was cooled and poured into ice-water and was made alkaline by careful addition of solid K2CO3. The product was extracted into ethyl acetate. The organic layer was washed with water, dried, concentrated and the residue was chromatographed, using a gradient of heptane/ethyl acetate as eluent, to provide 35 g of 6-methoxy-3,4-dihydroisoquinoline-1-carboxylic acid ethyl ester 5c. MS-ESI: [M+1] 234.14. NMR (CDCl3) δ 1.40 (t, 3, OC2H5), 2.72 (m, 2, CH2), 3.85 (s and m, 5, CH2 and OCH3) 4.40 (q, 2, OC2H5), 6.70, 6.80 and 7.70 (3×m, 3, Ar—H).

Workup

  1. temperaturewas heated
  2. customto obtain a homogeneous mixture
  3. temperaturethe temperature was raised again to 80° C.
  4. distillationwhile distilling off the CH2Cl2
  5. waitThe mixture was kept for 16 hr at 80° C. in order
  6. customthe cyclization reaction
  7. temperatureThen the reaction mixture was cooled
  8. extractionThe product was extracted into ethyl acetate
  9. washThe organic layer was washed with water
  10. customdried
  11. concentrationconcentrated
  12. customthe residue was chromatographed

Sources & evidence

ORD record
ord-8d388d6741bc4cbda51e2ecc45bef31f
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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