4-Methylmorpholine → (8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one

HRID 484394Notes

Reaction equation

HRID 484394 reaction equation
CC1(C)C2([CH2:10][S:11](O)(=[O:13])=[O:12])C(CC1CC2)=O.[CH3:16][O:17][C:18]1[CH:35]=[CH:34][C:33]2[C@H:32]3[N:23]([C:24](=[O:36])[C@@H:25]4[C@H:30]([CH2:31]3)[NH:29][CH2:28][CH2:27][CH2:26]4)[CH2:22][CH2:21][C:20]=2[CH:19]=1.CN1CCOCC1.CS(Cl)(=O)=O>C(Cl)Cl>[CH3:16][O:17][C:18]1[CH:35]=[CH:34][C:33]2[C@H:32]3[N:23]([C:24](=[O:36])[C@@H:25]4[C@H:30]([CH2:31]3)[N:29]([S:11]([CH3:10])(=[O:13])=[O:12])[CH2:28][CH2:27][CH2:26]4)[CH2:22][CH2:21][C:20]=2[CH:19]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 31297Methanesulfonyl chlorideHCID 9838835(8aS,12aS,13aS)-3-methoxy-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one

Product 1

HCID 10451421(8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

A mixture of 660 g of the d-10-camphorsulfonic acid salt of (8aS,12aS,13aS)-3-methoxy-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one (IA) in 8 litres of methylene chloride and 404 g of N-methylmorpholine was cooled in an ice bath to 10° C. and 153 ml of methanesulfonyl chloride was added over 30 minutes, allowing the temperature to rise to 16° C. The mixture was stirred at 10°-16° C. for 90 minutes, then washed sequentially with water, IN hydrochloric acid, and water. The organic layer was dried over sodium sulfate and the solvent removed under reduced pressure. The residue was crystallized from methanol to give (8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one, m.p. 138°-140° C.

Workup

  1. customto rise to 16° C
  2. washwashed sequentially with water, IN hydrochloric acid
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customthe solvent removed under reduced pressure
  5. customThe residue was crystallized from methanol

Sources & evidence

ORD record
ord-77874b2369b84a17aff2663e7defa0ec
Source dataset
uspto-grants-1993_07
Patent number
US05231181

Reaction notes

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