1,2-Dichloroethane → Cocaine

HRID 271030Notes

Reaction equation

HRID 271030 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[C@@H:12]([O:13][C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:15])[CH2:11][C@H:9]2[NH:10][C@@H:6]1[CH2:7][CH2:8]2)=[O:4].Cl.[CH2:23](N(CC)CC)C.C1(=O)OC(=O)CC1.C(Cl)CCl>C(Cl)Cl.O>[CH3:23][N:10]1[C@H:6]2[C@@H:5]([C:3]([O:2][CH3:1])=[O:4])[C@@H:12]([O:13][C:14]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[O:15])[CH2:11][C@@H:9]1[CH2:8][CH2:7]2

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 3046136Norcocaine hydrochloride

Product 1

HCID 446220Cocaine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of norcocaine hydrochloride (1 g, 3.07 mmol), triethylamine (0.86 ml, 6.14 mmol) in methylene chloride (20 ml) is treated with succinic anhydride (614 mg, 6.14 mmol) and the mixture heated at 45.degree. C. overnight, as described in U.S. Pat. No. 5,876,727. The solvents are removed under reduced pressure and the residue purified using silica gel flash chromatography (2:1 chloroform:methanol as the eluent). This gives succinylated norcocaine (1.0 g, 84%) as a thick syrup (3.beta.-(Benzoyloxy)-8-succinoyl-8-azabicyclo[3.2.1]octane-2.beta.-carboxylic acid methyl ester). To a solution of the acid (14 mg, 0.036 mmol) in distilled water (1 ml) at 0.degree. C., EDC (10.4 mg, 0.055 mmol) was added. After 5 minutes a solution of Qβ VLP in PBS (1 ml) is added dropwise and the mixture is allowed to warm to ambient temperature overnight. The conjugate is purified by dialysis against PBS and the degree of conjugation analyzed by mass spectral analysis. The resultant conjugate is used to immunize individuals.

Workup

  1. temperaturethe mixture heated at 45.degree
  2. customovernight
  3. customThe solvents are removed under reduced pressure
  4. customthe residue purified
  5. additionAfter 5 minutes a solution of Qβ VLP in PBS (1 ml) is added dropwise
  6. customThe conjugate is purified by dialysis against PBS

Sources & evidence

ORD record
ord-13a77ecef2a44988ba5a015340e28018
Source dataset
uspto-grants-2008_11
Patent number
US07452541B2

Reaction notes

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