Water → Methyl-(2-pyridin-3-yl-cyclohex-1-enylmethyl)amine hydrochloride

HRID 131527Notes

Reaction equation

HRID 131527 reaction equation
S(Cl)([Cl:3])=O.Cl.[CH3:6][NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]1([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)O.Cl[Si](C)(C)C.O>C(O)C.C(OCC)(=O)C>[ClH:3].[CH3:6][NH:7][CH2:8][C:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=1[C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6397ChlorotrimethylsilaneHCID 24386Thionyl ChlorideHCID 692224012-Methylaminomethyl-1-pyridin-3-yl-cyclohexanol hydrochloride

Product 1

HCID 69221531Methyl-(2-pyridin-3-yl-cyclohex-1-enylmethyl)amine hydrochloride

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

26 ml thionyl chloride were added dropwise to 5.20 g 2-methylaminomethyl-1-pyridin-3-yl-cyclohexanol hydrochloride and the mixture was heated (bath temperature 65 ° C) for 90 minutes, while stirring, and then concentrated under a water pump. After cooling, dilute sodium hydroxide solution (2 mol/l) was added, the mixture was extracted repeatedly with a mixture of equal volumes of tetrahydrofuran and ethyl acetate, the combined extracts were dried over magnesium sulfate and filtered and the filtrate was concentrated. The crude product obtained (3.25 g) was dissolved in 25 ml absolute ethanol and 8 ml ethyl acetate, and 4.1 ml chlorotrimethylsilane and 0.58 ml water were added in succession. The solid which had precipitated out (1.84 g) was filtered off with suction (cf. Example 79), the mother liquor was rendered basic with dilute sodium hydroxide solution (2 mol/l) and extracted repeatedly with a mixture of equal volumes of tetrahydrofuran and ethyl acetate, the combined extracts were dried over magnesium sulfate and filtered and the filtrate was concentrated. The residue obtained (1.45 g) was chromatographed on silica gel with methanol, to which 0.05 percent by volume of aqueous ammonia solution (25 percent strength by weight) had been added. The product fraction (0.52 g) was dissolved in 50 ml ethyl acetate, and 0.66 ml chlorotrimethylsilane, followed by 92 μl water, were added. 0.57 g methyl-(2-pyridin-3-yl-cyclohex-1-enylmethyl)amine hydrochloride was obtained as a precipitate.

Workup

  1. concentrationconcentrated under a water pump
  2. temperatureAfter cooling
  3. additiondilute sodium hydroxide solution (2 mol/l) was added
  4. extractionthe mixture was extracted repeatedly with a mixture of equal volumes of tetrahydrofuran and ethyl acetate
  5. dry with materialthe combined extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customThe crude product obtained (3.25 g)
  9. customThe solid which had precipitated out (1.84 g)
  10. filtrationwas filtered off with suction (cf. Example 79)
  11. extractionextracted repeatedly with a mixture of equal volumes of tetrahydrofuran and ethyl acetate
  12. dry with materialthe combined extracts were dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated
  15. customThe residue obtained (1.45 g)
  16. customwas chromatographed on silica gel with methanol, to which 0.05 percent by volume of aqueous ammonia solution (25 percent strength by weight)
  17. additionhad been added
  18. dissolutionThe product fraction (0.52 g) was dissolved in 50 ml ethyl acetate
  19. additionwere added

Sources & evidence

ORD record
ord-705d38b2d4c74ddcb0e42cff0c1cc72d
Source dataset
uspto-grants-2008_06
Patent number
US07384961B2

Reaction notes

Loading…