Hydrochloric Acid → HCID 67924803, compound

HRID 359458Notes

Reaction equation

HRID 359458 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:2]=12.C([Li])CCC.[C:17]1([CH3:25])[CH:22]=[CH:21][C:20]([CH:23]=[O:24])=[CH:19][CH:18]=1.[ClH:26]>O1CCCC1.CCCCCC.CCOCC.O>[ClH:26].[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([CH:23]([C:20]3[CH:21]=[CH:22][C:17]([CH3:25])=[CH:18][CH:19]=3)[OH:24])[C:2]=12

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 77254-MethylbenzaldehydeHCID 816166,7,8,9-Tetrahydro-5H-cyclohepta[b]pyridineHCID 178418339Butyllithium

Product 1

HCID 67924803HCID 67924803, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-10 °C

Procedure

6,7,8,9-Tetrahydro-5H-cyclohepta[b] pyridine (7.4g 0.05m) in tetrahydrofuran (100ml) was cooled to -10° C. and treated with a 1.57M solution of n-butyl lithium in n-hexane (32ml), then stirred at -10° C. for a further 0.5h. 4-Tolualdehyde (10g, 0.083m) in tetrahydrofuran (10ml) was added rapidly and the mixture allowed to warm to room temperature, then water and ether were added. The combined ether extracts were treated with 2N hydrochloric acid and the separated aqueous acid extract was basified with solid sodium carbonate and then extracted with chloroform. The combined chloroform solutions were washed with water, dried (MgSO4) and evaporated to give an oil. This was purified by chromatography using silica columns eluted with DIPE or chloroform. The purification was monitored by t.l.c. using DIPE and chloroform on silica plates or samples were silylated with 1-(trimethylsilyl)-imidazole and injected on a g.l.c. (injection temp. 200° C.) with a 25 meter BPI column, running a temperature programme from 120 ° to 300° C. at 10° C./min., then isothermal and carrier gas helium at 10psi. The products were isolated and these were converted into the hydrochloride salts by dissolving in ether and treating with ethereal HCl to give R*, S* 1-(6,7,8,9-tetrahydro-5H-cyclohepta-[b] pyrid-9-yl)-1-(4-methylphenyl) methanol hydrochloride (retention time 16.72 min, 1.4g, 9%) m.p. 205°-7° C. (Found: C, 71.4;H, 7.5; N, 4.6; C18H21NO.HCl requires C, 71.2;H, 7.3; N, 4.6%). R*, R* 1-(6,7,8,9-tetrahydro-5H-cyclohepta[b] pyrid-9yl)-1-(4-methylphenyl) methanol, hydrochloride, three quarter hydrate (retention time 16.63 min, 1.7g, 11%) m.p. 216°-7° C. (Found C, 68.6; H, 7.3; N, 4.35, C18H21NO.HCl. 0.75H2O requires C, 68.1; H, 7.5; N, 4.4%).

Workup

  1. temperatureto warm to room temperature
  2. extractionthe separated aqueous acid extract
  3. extractionextracted with chloroform
  4. washThe combined chloroform solutions were washed with water
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give an oil
  8. customThis was purified by chromatography
  9. washeluted with DIPE or chloroform
  10. customThe purification
  11. custom(injection temp. 200° C.)
  12. customfrom 120 ° to 300° C.
  13. customThe products were isolated

Sources & evidence

ORD record
ord-dfcfdaa148d24f97b823057230b8da6b
Source dataset
uspto-grants-1991_03
Patent number
US05001131

Reaction notes

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