trans-3,4,4a,5,10,10a-hexahydro-9-iodo-6-methoxy-4-methyl-2H-naphth[2,3-b]-1,4-oxazine → Sdz nvi-085

HRID 542177Notes

Reaction equation

HRID 542177 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]([O:17][CH3:18])=[C:6]2[C:16]=1[CH2:15][C@H:9]1[O:10][CH2:11][CH2:12][N:13]([CH3:14])[C@@H:8]1[CH2:7]2.[CH3:19][S:20][Li]>CN(C=O)C>[CH3:18][O:17][C:5]1[CH:4]=[CH:3][C:2]([S:20][CH3:19])=[C:16]2[C:6]=1[CH2:7][C@H:8]1[N:13]([CH3:14])[CH2:12][CH2:11][O:10][C@@H:9]1[CH2:15]2

Participants

4

Reactant 2

HCID 15131080trans-3,4,4a,5,10,10a-hexahydro-9-iodo-6-methoxy-4-methyl-2H-naphth[2,3-b]-1,4-oxazineHCID 178418898HCID 178418898, compound

Product 1

HCID 128503Sdz nvi-085

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

0.44 g (1.2 mM) of trans-3,4,4a,5,10,10a-hexahydro-9-iodo-6-methoxy-4-methyl-2H-naphth[2,3-b]-1,4-oxazine (for production see example 1), dissolved in 5 ml of DMF, as well as 2.34 g (16.3 mM) of copper-I-oxide, are added to a suspension of 0.53 g (9.8 mM) of methylthiolithium in 10 ml of dimethylformamide. The reaction mixture is subsequently stirred for 5 hours at 80° under an argon atmosphere. The preparation is then filtered through Hyflo, washed with 20 ml of methylene chloride, and the filtrate is concentrated by evaporation. The residue is taken up in 30 ml of methylene chloride/30 ml of ice water, the organic phase is separated, and the aqueous phase is extracted three times, each with 10 ml of methylene chloride. The combined organic phases are dried and concentrated by evaporation. Trans-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-methylthio-2H-naphth[2,3-b]-1,4-oxazine is obtained as an oil. The oil is purified by chromatography (silica gel, methylene chloride, 5% methanol). 1-H-NMR 90 MHz (CDCl3): δ=2.36 (s; 3H, N--CH3), 2.42 (s; 3H, S--CH3), 3.81 (s; 3H, O--CH3).

Workup

  1. filtrationThe preparation is then filtered through Hyflo
  2. washwashed with 20 ml of methylene chloride
  3. concentrationthe filtrate is concentrated by evaporation
  4. customthe organic phase is separated
  5. extractionthe aqueous phase is extracted three times
  6. customThe combined organic phases are dried
  7. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-d64e5834da3845888dd6c51312d74c28
Source dataset
uspto-grants-1987_04
Patent number
US04656167

Reaction notes

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