Hydrochloric Acid → Naloxone

HRID 2413125Notes

Reaction equation

HRID 2413125 reaction equation
Cl.[CH2:2]([N:5]1[CH2:23][CH2:22][C@:12]23[C:13]4[C:14]5[O:21][C@H:11]2[C:10](=[O:24])[CH2:9][CH2:8][C@@:7]3([OH:25])[C@H:6]1[CH2:19][C:18]=4[CH:17]=[CH:16][C:15]=5[OH:20])[CH:3]=[CH2:4].Cl.C(OC(=O)[C@H](CS)N)C.Cl>N1C=CC=CC=1.C(OCC)C.C(O)C>[CH2:4]=[CH:3][CH2:2][N:5]1[C@@H:6]2[CH2:19][C:18]3[CH:17]=[CH:16][C:15]([OH:20])=[C:14]4[O:21][C@H:11]5[C:10]([CH2:9][CH2:8][C@:7]2([OH:25])[C@:12]5([C:13]=34)[CH2:22][CH2:23]1)=[O:24]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 2723617Ethyl cysteinate hydrochlorideHCID 5464092Naloxone Hydrochloride

Product 1

HCID 5284596Naloxone

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1049PyridineSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of 4 mmol of 17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride (naloxone hydrochloride 1.46 g) and of 8 mmol cysteine ethyl ester hydrochloride (1.5 g) in 45 ml of dry pyridine is stirred at room temperature for 20 hours under a nitrogen atmosphere. The solution is concentrated in vacuo. The resulting mixture is partitioned between water (50 ml) and chloroform (50 ml). The pH of the aqueous layer is adjusted to 7.0 with 10% NaOH. After shaking, the organic layer is separated. The aqueous layer obtained is extracted twice with 50 ml of chloroform. The organic layers are combined, washed once with water, dried over sodium sulfate and evaporated to give a colorless oil. The oil is purified on a chromatographic column [neutral silica gel (silicAR CC-7), 100 g] using a mobile phase of a mixed solvent of chloroform and methanol (50:1). The selected fractions are collected and evaporated in vacuo to give a colorless oil. The oil is dissolved in 30 ml dry ethyl ether (30 ml) and excess hydrogen chloride in dry ethanol is added. The colorless powder obtained is filtered and dried over phosphorus pentoxide to give 6-spirothiazolidine dihydrochloride of naloxone as an amorphous powder; m.p. 171°-175° C. (dec). Elemental analysis for C24H30N2O5S.2HCl.2H2O calcd.: C, 50.79; H, 6.39; N, 4.94; S, 5,65; Cl, 12.49. Found: C, 50.55; H, 6.26; N, 4.97; S, 5.74; Cl, 12.56. IR (KBr) cm-1 : 1750, 1650, 1640, 1630, 1620, 1510, 1470, 1460, 1375, 1320, 1230, 1120, 1030, 950 and 900. NMR (DMSO-d6) δ 1.0-4.0 (m), 4.24 (2H, q, J=Hz, --COOCH2), 4.72 (1H, t, J-8 Hz, 4'-H), 5.02 and 5.14 (1/3H and 2/3H, respectively, each s, 5-H), 5.2-6.0 (m), 6.6-6.9 (2H, m, aromatic protons).

Workup

  1. concentrationThe solution is concentrated in vacuo
  2. customThe resulting mixture is partitioned between water (50 ml) and chloroform (50 ml)
  3. customthe organic layer is separated
  4. customThe aqueous layer obtained
  5. extractionis extracted twice with 50 ml of chloroform
  6. washwashed once with water
  7. dry with materialdried over sodium sulfate
  8. customevaporated
  9. customto give a colorless oil
  10. customThe oil is purified on a chromatographic column [neutral silica gel (silicAR CC-7), 100 g]
  11. customThe selected fractions are collected
  12. customevaporated in vacuo
  13. customto give a colorless oil
  14. customThe colorless powder obtained
  15. filtrationis filtered
  16. dry with materialdried over phosphorus pentoxide

Sources & evidence

ORD record
ord-dad2f9ee151349849d0a82d46a2869b2
Source dataset
uspto-grants-1985_01
Patent number
US04496570

Reaction notes

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