Ammonium Chloride → HCID 11362817, compound

HRID 1441522Notes

Reaction equation

HRID 1441522 reaction equation
[NH4+].[Cl-].Cl.[CH:4]1([CH2:7][N:8]2[CH2:25][CH2:24][C@:15]34[C:16]5[C:17]6[O:23][C@H:14]3[C:13](=[O:26])[CH2:12][CH2:11][C@@:10]4([O:27][CH2:28][CH2:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C@H:9]2[CH2:22][C:21]=5[CH:20]=[CH:19][CH:18]=6)[CH2:6][CH2:5]1>CO.[Zn]>[CH:4]1([CH2:7][N:8]2[CH2:25][CH2:24][C@@:15]34[C:16]5[C:17]([OH:23])=[CH:18][CH:19]=[CH:20][C:21]=5[CH2:22][C@@H:9]2[C@:10]3([O:27][CH2:28][CH2:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH2:11][CH2:12][C:13](=[O:26])[CH2:14]4)[CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 68536012HCID 68536012, compound

Product 1

HCID 11362817HCID 11362817, compoundYield 99.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

NH4Cl (0.72 g, 13.46 mmol) was added to a reflux boiling solution of 54 (1.2 g, 2.71 mmol) in 50 ml MeOH under stirring. 0.88 g (13.46 mmol) activated zinc powder was added in small portions to this mixture. This mixture was stirred under reflux for 80 min., then cooled to room temperature and filtered off from the inorganic residue. The inorganic residue was washed with hot methanol and the filtrate evaporated down. 50 ml H2O was added to the evaporation residue which was then alkalised with conc. NH4OH. This mixture was extracted with CH2Cl2 (3×80 ml), the combined organic phases washed with saturated NaCl solution (5×100 ml), dried over Na2SO4 and evaporated down. 1.20 g (99%) of 17-(cyclopropylmethyl)-4-hydroxy-14β-[(3-phenylpropyl)oxy]morphinan-6-one (55) was obtained as a yellowish oil which was used for the next reaction step without further purification. For analytical purposes 0.08 g of the oil was dissolved in ether and after the addition of etherial HCl 0.059 g of 0.17-(cyclopropylmethyl)-4-hydroxy-14β-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride (55.HCl) was isolated as a colourless powder. Fp. >170° C. (decomposition); MS (CI): m/z 446 (M++1); IR (KBr): 1709 (C═O) cm−1; 1H-NMR (DMSO-d6): δ 9.82 (s, 1H, C4-OH), 8.43 (s, wide, 1H, +N17-H), 7.30-7.20 (m, 5 arom. H, C14-O(CH2)3Ph), 7.03 (t, J=8.0 Hz, 1 arom. H, C2-H), 6.66 (m, 2 arom. H), 4.40 (ps-d, C9-H), 1.09 (m, 1H, N17-CH2CH(CH2)2), 0.70-0.67 (m, 2H, N17-CH2CH(CH2)2), 0.52-0.40 (m, 2H, N17-CH2CH(CH2)2).

Workup

  1. additionwas added in small portions to this mixture
  2. stirringThis mixture was stirred
  3. temperatureunder reflux for 80 min.
  4. filtrationfiltered off from the inorganic residue
  5. washThe inorganic residue was washed with hot methanol
  6. customthe filtrate evaporated down
  7. addition50 ml H2O was added to the evaporation residue which
  8. extractionThis mixture was extracted with CH2Cl2 (3×80 ml)
  9. washthe combined organic phases washed with saturated NaCl solution (5×100 ml)
  10. dry with materialdried over Na2SO4
  11. customevaporated down

Sources & evidence

ORD record
ord-4e26c6ae03e8453399e013a51498c582
Source dataset
uspto-grants-2010_02
Patent number
US07655671B2

Reaction notes

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