Dichloromethane → HCID 69228552, compound

HRID 723393Notes

Reaction equation

HRID 723393 reaction equation
[OH:1][C@@H:2]1[C:11]2[CH:10]=[CH:9][N:8]3[C:12]([CH3:18])=[C:13]([CH2:15][O:16][CH3:17])[N:14]=[C:7]3[C:6]=2[NH:5][C@H:4]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:3]1[OH:25].CS(O)(=O)=O.ClCCl>COCCO>[OH:25][C@H:3]1[C@@H:2]([O:1][CH2:13][CH2:15][O:16][CH3:17])[C:11]2[CH:10]=[CH:9][N:8]3[C:12]([CH3:18])=[C:13]([CH2:15][O:16][CH3:17])[N:14]=[C:7]3[C:6]=2[NH:5][C@@H:4]1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1.[OH:25][C@H:3]1[C@H:2]([O:1][CH2:13][CH2:15][O:16][CH3:17])[C:11]2[CH:10]=[CH:9][N:8]3[C:12]([CH3:18])=[C:13]([CH2:15][O:16][CH3:17])[N:14]=[C:7]3[C:6]=2[NH:5][C@@H:4]1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 6395Methanesulfonic AcidHCID 10215337HCID 10215337, compound

Product 2

HCID 69228552HCID 69228552, compoundYield 36%HCID 69229874HCID 69229874, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
55 °C

Procedure

2.0 g of (7R,8R,9R)-7,8-dihydroxy-2-methoxymethyl-3-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine are dissolved in 50 ml 2-methoxyethanol and 1 ml of methane sulfonic acid is slowly added. The reaction is heated at 55° C. for 3 h and subsequently poured onto 80 ml icewater and 100 ml dichloromethane. The organic layer is separated and the aqueous phase extracted three times with dichloromethane. The combined organic phases are dried over anhydrous sodium sulfate and the solvent removed in vacua. The two diastereomers are separated by column chromatography on silica gel (eluent: diethyl ether) to afford 850 mg (36%) of (7S,8R,9R)-8-hydroxy-7-(2-methoxyethoxy)-2-methoxymethyl-3-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine (28a, m.p. 63–65° C.) and 400 mg (17%) of (7R,8R,9R)-8-hydroxy-7-(2-methoxyethoxy)-2-methoxymethyl-3-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine (28b, m.p. 50–53° C.).

Workup

  1. customThe organic layer is separated
  2. extractionthe aqueous phase extracted three times with dichloromethane
  3. dry with materialThe combined organic phases are dried over anhydrous sodium sulfate
  4. customthe solvent removed in vacua
  5. customThe two diastereomers are separated by column chromatography on silica gel (eluent: diethyl ether)

Sources & evidence

ORD record
ord-c249207649ec41dca83b412772d39e4f
Source dataset
uspto-grants-2006_11
Patent number
US07141567B2

Reaction notes

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