Hydrogen Bromide → Tazadolene

HRID 1906421Notes

Reaction equation

HRID 1906421 reaction equation
O[CH2:2][CH2:3][CH2:4][NH:5][C@@H:6]1[CH2:11][CH2:10][CH2:9][CH2:8][C@@H:7]1[CH:12](O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Br.[OH-].[Na+]>C1(C)C=CC=CC=1>[C:13]1(/[CH:12]=[C:7]2/[CH:6]([N:5]3[CH2:4][CH2:3][CH2:2]3)[CH2:11][CH2:10][CH2:9][CH2:8]/2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 14798Sodium HydroxideHCID 54313545HCID 54313545, compound

Product 1

HCID 6435466TazadoleneYield 31.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2.5 g (9.5 mmoles) of cis-N-(3-hydroxypropyl)-N-[2-[hydroxy(phenyl)methyl]cyclohexyl]amine, 10 ml of toluene and 6.45 g of 48% v/v aqueous hydrogen bromide solution was stirred and heated on a steam bath for 3.5 hr. The resulting solution was cooled, basified with 20% sodium hydroxide solution and extracted with chloroform. The chloroform extract was washed with water, and saturated sodium chloride solution and then dried over magnesium sulfate and evaporated. The residue, 2 g, was chromatographed by high pressure liquid chromatography (HPLC) procedures using a Merck silica gel, size C column and 10% v/v methanol/in chloroform/1% v/v ammonium hydroxide mixture as eluting liquid, collecting 20 ml fractions. Fractions 1 to 14 gave no product material. Fractions 15 to 25 gave 0.686 g (30% yield) of (±)-(E)-1-[2-(phenylmethylene)cyclohexyl]azetidine, which was identified by NMR analysis comparison with the NMR of standard, authentic compound. Fractions 26 to 31 gave 0.25 g of a mixture, and fractions 32 to 50 gave 0.286 g of N-(3-hydroxypropyl)-N-[2-(phenylmethylene)cyclohexyl]amine which was identified by NMR comparison with a known standard sample, and also by conversion to its hydrochloride salt which was identical to a standard sample by NMR, UV and IR spectral analysis comparisons.

Workup

  1. temperatureheated on a steam bath for 3.5 hr
  2. temperatureThe resulting solution was cooled
  3. extractionextracted with chloroform
  4. extractionThe chloroform extract
  5. washwas washed with water, and saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. customevaporated
  8. customThe residue, 2 g, was chromatographed by high pressure liquid chromatography (HPLC) procedures
  9. washas eluting liquid
  10. customcollecting 20 ml fractions
  11. customFractions 1 to 14 gave no product material

Sources & evidence

ORD record
ord-dd23ca2baf884864b29e5a6e559d74ba
Source dataset
uspto-grants-1987_03
Patent number
US04652559

Reaction notes

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