Dimethylformamide → HCID 86613658, compound

HRID 369001Notes

Reaction equation

HRID 369001 reaction equation
Cl.[O:2]1[C@:14]2([CH3:20])[C@@:15]34[CH2:17][CH2:18][NH:19][C@@H:9]([C@:10]3([O:22][CH3:23])[CH2:11][CH2:12][C:13]2=[O:21])[CH2:8][C:7]2=[C:16]4[C:3]1=[C:4]([O:24][CH3:25])[CH:5]=[CH:6]2.C(=O)([O-])[O-].[K+].[K+].[C:32]1([CH2:38][CH2:39][Br:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CN(C)C=O>O>[BrH:40].[O:2]1[C@:14]2([CH3:20])[C@@:15]34[CH2:17][CH2:18][N:19]([CH2:39][CH2:38][C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[C@@H:9]([C@:10]3([O:22][CH3:23])[CH2:11][CH2:12][C:13]2=[O:21])[CH2:8][C:7]2=[C:16]4[C:3]1=[C:4]([O:24][CH3:25])[CH:5]=[CH:6]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7666Phenethyl bromideHCID 11430Potassium CarbonateHCID 69035111HCID 69035111, compound

Product 1

HCID 86613658HCID 86613658, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4,5α-epoxy-3,14-dimethoxy-5-methylmorphinan-6-one hydrochloride (H. Schmidhammer et al., Helv. Chim. Acta Vol. 77:1585-1589, 1994) (2.24 g, 6.12 mmol), potassium carbonate (3.0 g, 21.9 mmol), 2-phenylethyl bromide (1.05 ml, 7.74 mmol), and 15 ml of anhydrous N,N-dimethyl formamide was stirred at 80° C. (bath temperature) for 2 h. After cooling and addition of 110 ml of H2O, the mixture was extracted with diethyl ether (3×60 ml). The combined organic layers were washed with H2O(3×70 ml), dried over Na2SO4 and evaporated. The residue (2.9 yellow oil) was converted into the hydrobromide salt in the usual way and crystallized from MeOH to give 1.4 g (63%) of 4,5α-epoxy-3,14-dimethoxy-5-methyl-17-(2-phenyl)ethylmorphinan-6-one hydrobromide (compound 7) as colorless crystals. A small portion of this material was recrystallized from MeOH for analyses. M.p. 94-96° C. IR (KBr): 3400 (+NH), 1720 (CO) cm-1. CI-MS: m/z 434 (M+ +1). 1H-NMR (DMSO-d6) δ 10.15 (s, +NH), 7.30 (m, 5 arom. H), 6.74 (d, J=8.2 Hz, 1 arom. H), 6.68 (d, J=8.2 Hz, 1 arom.), 3.87 (s, OCH3 --C(3)), 3.58 (s, OCH3 --C(14)), 1.60 (s, CH3 --C(5)). Analysis calculated for C27H31NO4. HBr (514.44): C 63.04, H 6.27, N 2.72; found: C 63.18, H 6.60, N 2.39. A solution of the compound 7 (1.4 g, 3.32 mmol) in 5 ml of 48% HBr was refluxed for 30 min and then evaporated. The residue was dissolved in MeOH and again evaporated (this operation was repeated once) to afford a brownish crystalline residue (1.8 g) which was treated with hot MeOH to yield 590 mg (42%) of the compound 8.HBr. A small portion was recrystallized for analyses. M.p.>316° C. IR (KBr):3400 (+NH, OH), 1722 (CO)cm-1. CI-MS: m/z 420 (M+ +1). 1H-NMR (DMSO-d6) δ 8.95 and 8.45 (2s, +NH,OH), 6.90 (m, 5 arom. H), 6.23 (dd, J=8.2, 8.2 Hz, 2 arom. H), 2.97 s, OCH3), 1.08 (s, CH3 --C(5)). Analysis calculated for C26H29NO4. HBr. 0.2 MeoH (506.85): C 62.09, H 6.13, N 2.76, Br 16.77; found: C 61.79, H 6.18, N 2.63, Br 16.12.

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture was extracted with diethyl ether (3×60 ml)
  3. washThe combined organic layers were washed with H2O(3×70 ml)
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customcrystallized from MeOH

Sources & evidence

ORD record
ord-13c9e49e8e7d4056a9e3fcfe8764fd48
Source dataset
uspto-grants-2000_10
Patent number
US06136817

Reaction notes

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