Iodine → HCID 69314272, compound

HRID 1293511Notes

Reaction equation

HRID 1293511 reaction equation
[H-].[Na+].[CH:3]1[C:19]2[CH2:18][C@H:17]3[N:20]([CH2:22][CH2:23][C@@:9]45[C@H:16]3[CH:15]=[CH:14][C@H:12]([OH:13])[C@@H:10]4[O:11][C:7]([C:8]=25)=[C:5]([OH:6])[CH:4]=1)[CH3:21].Br[CH2:25][CH2:26][CH2:27][N:28]1[C:32](=[O:33])[C:31]2=[CH:34][CH:35]=[CH:36][CH:37]=[C:30]2[C:29]1=[O:38].II>O.CO>[C:29]1(=[O:38])[N:28]([CH2:27][CH2:26][CH2:25][O:6][C:5]2[CH:4]=[CH:3][C:19]3[CH2:18][C@H:17]4[N:20]([CH3:21])[CH2:22][CH2:23][C@:9]56[C:8]=3[C:7]=2[O:11][C@H:10]5[C@@H:12]([OH:13])[CH:14]=[CH:15][C@@H:16]46)[C:32](=[O:33])[C:31]2=[CH:34][CH:35]=[CH:36][CH:37]=[C:30]12

Participants

7

Reactant 4

HCID 807IodineHCID 21611N-3-BromopropylphthalimideHCID 24758Sodium hydride2×HCID 5288826Morphine

Product 1

HCID 69314272HCID 69314272, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

1.5 g (37.5 mmol) of NaH (60% dispersion in mineral oil) was rinsed with 2×25 mL of hexanes to remove the oil. To the reaction mixture was added 140 mL of anhydrous DMF followed by 10.1 g (35 mmol) of morphine. This mixture was allowed to stir at room temperature for 30 minutes under nitrogen atmosphere, and 14.5 g (53 mmol) of N-(3-bromopropyl) phthalimide was added. The reaction mixture was allowed to stir 18 h at room temperature. The reaction was monitored by thin layer chromatography (silica, 7:2:1:1, MeOH:EtAc:NH40H:H2O, I2 visualization), which showed that the reaction was incomplete. To the reaction mixture 0.15 g (3.75 mmol) of NaH (60% in oil) was added, and the mixture was allowed to stir for an additional 1.5 h. The mixture was poured into 350 mL of ice-water and extracted with 250 mL of ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with 2×250 mL of ethyl acetate. The organic layers were combined and washed with 2×150 mL of water, 150 mL of 1N NaOH and 2×150 mL of water. The organic layer was dried (Na2SO4) and concentrated. The residue was crystallized with diethyl ether to give 12.9 g (27.3 mmol, 77%) of the desired product 13 as a white solid.

Workup

  1. customto remove the oil
  2. additionTo the reaction mixture was added 140 mL of anhydrous DMF
  3. stirringto stir 18 h at room temperature
  4. stirringto stir for an additional 1.5 h
  5. extractionextracted with 250 mL of ethyl acetate
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with 2×250 mL of ethyl acetate
  8. washwashed with 2×150 mL of water, 150 mL of 1N NaOH and 2×150 mL of water
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. concentrationconcentrated
  11. customThe residue was crystallized with diethyl ether

Sources & evidence

ORD record
ord-35d8244312234f78ba0dc7391b4d1b4b
Source dataset
uspto-grants-2007_07
Patent number
US07238791B1

Reaction notes

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