Methylamine → HCID 15482079, compound

HRID 1358690Notes

Reaction equation

HRID 1358690 reaction equation
[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH:3]1[C:4]([C:10](OC)=O)=[CH:5][CH2:6]2.C1(C#[N:22])C=CC=CC=C1.CN.[OH-].[Na+]>CO>[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH:3]1[C:4]([C:10]#[N:22])=[CH:5][CH2:6]2

Participants

6

Reactant 4

HCID 6329MethylamineHCID 14798Sodium HydroxideHCID 1395162,4,6-Cycloheptatriene-1-carbonitrileHCID 592280methyl 8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate

Product 1

HCID 15482079HCID 15482079, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The reaction scheme C shown below is an example of reaction scheme for synthesizing an anhydro-ecgonine derivative (the formula 3) and a phenyltropane derivative (the formula 6) without producing cocaine as an intermediate. In detail, the reaction scheme C is a scheme in which methyl (1RS)-8-methyl-8-azabicyclo-[3.2.1]oct-2-ene-2-carboxylate (7: (1RS)-AECG; such an abbreviation of a compound name is hereinafter described in a parenthesis and properly used) is synthesized, and then a fluoropropyl group is introduced thereinto at the N-8 position to synthesize methyl [1RS-(2-exo,3-exo)]-8-(3-fluoropropyl)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate (12: (1RS)-β-CIT-FP). Specifically, 2,4,6-cycloheptatriene-1-carbonitrile (4: CHT-CN) is allowed to react with methylamine in methanol solvent in the presence of sodium hydroxide to obtain (1RS)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carbonitrile (6: (1RS)-AECG-CN). The cyano group of this compound is hydrolyzed and then converted to a methyl ester group to obtain methyl (1RS)-8-methyl-8-azabicyclo[3.2.1)oct-2-ene-2-carboxylate (7: (1RS)-AECG), which is allowed to react with phenylmagnesium bromide (PhMgBr) by a well-known method to obtain methyl [1RS-(2-exo,3-exo)]-3-phenyl-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate (8: (1RS)-β-CPT). The tropane portion of this compound is converted to nortropane at the N-8 position, followed by substitution by a fluoropropane group at the N-8 position, whereby (1RS)-β-CIT-FP 12 can be obtained. optically active (1R)-β-CIT-FP can be obtained by optical resolution of (1RS)-β-CIT-FP 12 or by subjecting (1RS)-nor-β-CIT 11 to optical resolution to obtain an optically active substance in the course of the synthesis and continuing reactions shown in Reaction scheme C.

Workup

  1. customIn detail, the reaction scheme C
  2. customis synthesized
  3. additiona fluoropropyl group is introduced

Sources & evidence

ORD record
ord-610c86211fc94c57b3b830f4c61628c0
Source dataset
uspto-grants-2003_07
Patent number
US06596868B2

Reaction notes

Loading…