Ethyl Acetate → HCID 69314272, compound

HRID 1282902Notes

Reaction equation

HRID 1282902 reaction equation
[CH:1]1[C:17]2[CH2:16][C@H:15]3[N:18]([CH2:20][CH2:21][C@@:7]45[C@H:14]3[CH:13]=[CH:12][C@H:10]([OH:11])[C@@H:8]4[O:9][C:5]([C:6]=25)=[C:3]([OH:4])[CH:2]=1)[CH3:19].CC(C)([O-])C.[K+].Br[CH2:29][CH2:30][CH2:31][N:32]1[C:36](=[O:37])[C:35]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]2[C:33]1=[O:42].C(OCC)(=O)C>CN(C)P(N(C)C)(N(C)C)=O>[C:33]1(=[O:42])[N:32]([CH2:31][CH2:30][CH2:29][O:4][C:3]2[CH:2]=[CH:1][C:17]3[CH2:16][C@H:15]4[N:18]([CH3:19])[CH2:20][CH2:21][C@:7]56[C:6]=3[C:5]=2[O:9][C@H:8]5[C@@H:10]([OH:11])[CH:12]=[CH:13][C@@H:14]46)[C:36](=[O:37])[C:35]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]12

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 21611N-3-BromopropylphthalimideHCID 5288826MorphineHCID 23665647Potassium tert-butoxide

Product 1

HCID 69314272HCID 69314272, compound

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent

Procedure

A stirred solution of 25.0 g (87.7 mmol) of morphine in 350 ml of hexamethylphosphoramide was cooled in an ice-water bath and 10.3 g (92.0 mmol) of potassium tertiary butoxide was added through a Gooch tube over a period of 10 minutes. After stirring at room temperature for 0.5 hr, 23.5 g (87.7 mmol) of N-(3-bromopropyl)-phthalimide was added and stirring was continued at this temperature for 21 hrs. The reaction mixture was poured into 500 ml of ice-water and then 500 ml of ethyl acetate was added. The organic phase was separated and the aqueous solution was extracted with 500 ml of ethyl acetate. The combined ethyl acetate extracts were washed with water (3 × 250 ml), 2 N sodium hydroxide, and with water (3 × 300 ml). After drying, the solvent was removed in vacuo to give 31.0 g of crude product, which after recrystallization from isopropanol--ether, yielded pure 3-(3-phthalimidopropoxy)-7,8-didehydro-4,5 α-epoxy-17-methylmorphinan-6 α-ol, m.p. 121°-123°, [α]D25 -76.63° (c 1.03, MeOH).

Workup

  1. stirringstirring
  2. waitwas continued at this temperature for 21 hrs
  3. customThe organic phase was separated
  4. extractionthe aqueous solution was extracted with 500 ml of ethyl acetate
  5. washThe combined ethyl acetate extracts were washed with water (3 × 250 ml), 2 N sodium hydroxide
  6. customAfter drying
  7. customthe solvent was removed in vacuo
  8. customto give 31.0 g of crude product, which
  9. customafter recrystallization from isopropanol

Sources & evidence

ORD record
ord-0d974d87a13a499db0e4bdbea0979211
Source dataset
uspto-grants-1976_08
Patent number
US03972992

Reaction notes

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