Formaldehyde → (+)-Glaucine

HRID 427425Notes

Reaction equation

HRID 427425 reaction equation
[CH3:1][O:2][C:3]1[CH:23]=[C:22]2[C:6]3[C@@H:7]([NH:19][CH2:20][CH2:21]2)[CH2:8][C:9]2[C:14]([C:5]=3[C:4]=1[O:24][CH3:25])=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=2.[CH2:26]=O.[BH4-].[Na+]>CO>[CH3:26][N:19]1[C@H:7]2[CH2:8][C:9]3[C:14](=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH3:18])[CH:10]=3)[C:5]3[C:6]2=[C:22]([CH:23]=[C:3]([O:2][CH3:1])[C:4]=3[O:24][CH3:25])[CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 30835Laurelliptine, O,O'-dimethyl- (7CI)HCID 4311764Sodium borohydride

Product 1

HCID 16754(+)-GlaucineYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Norglaucine (1.90 g, 5.2 mmol), methanol (50 ml) and 35.5% formaldehyde (6.0 ml) were successively placed in a 250 ml reaction bottle. To the mixture, NaBH4 was added portionwise (total 2.0 g, 52 mmol) at room temperature while stirring. The mixture was then reacted for 6 hours, concentrated under reduced pressure, and fractionated between water (150 ml) and chloroform (150 ml×3). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to produce a solid which was purified by column chromatography (silica gel, with chloroform as the eluant) to obtain solid product glaucine (1.78 g, 90%). Physical data were as follows: mp: 112-114° C. (diethyl ether); [α]D24 +120.0° (c=0.30, MeOH); 1H NMR (CDCl3, 400 MHz) δ 8.06 (1H, s, H-11), 6.75 (1H, s, H-8), 6.56 (1H, s, H-3), 3.91 (3H, s, 9-OMe), 3.88 (3H, s, 10-OMe), 3.86 (3H, s, 2-OMe), 3.64 (3H, s, 1-OMe), 2.54 (3H, s, N-Me).

Workup

  1. customThe mixture was then reacted for 6 hours
  2. concentrationconcentrated under reduced pressure
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto produce a solid which
  8. customwas purified by column chromatography (silica gel

Sources & evidence

ORD record
ord-62916b7ce4a346b997cf4cbd4f19b592
Source dataset
uspto-grants-2001_11
Patent number
US06313134B1

Reaction notes

Loading…