Ammonia → HCID 131723337, compound

HRID 2188383Notes

Reaction equation

HRID 2188383 reaction equation
Cl.[CH3:2][N:3]([CH:5]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:12])[CH3:4].N.[CH2:21]([Mg][Cl:29])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[Cl-].[NH4+]>O1CCCC1.O>[ClH:29].[CH2:21]([C:7]1([OH:12])[CH2:8][CH2:9][CH2:10][CH2:11][CH:6]1[CH:5]([N:3]([CH3:2])[CH3:4])[C:13]1[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 22447907HCID 22447907, compoundHCID 178418336HCID 178418336, compound

Product 1

HCID 131723337HCID 131723337, compoundYield 63.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The base was freed from 3.2 g (11.2 mmole) of the hydrochloride of 2-[dimethylamino-(4-fluorophenyl)methyl]cyclohexanone obtained according to stage 1 with 30 ml of water and 10 ml of ammonia solution (25 vol. %), extracted three times with 30 ml of ether each time, and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator without heating (500 to 10 mbar). 2.69 g (10.8 mmole) of this base were dissolved in 10 ml of tetrahydrofuran, added dropwise while cooling in an ice bath to 6.5 ml (12.9 mmole) of benzylmagnesium chloride (2 M solution in tetrahydrofuran), and the whole was stirred for 15 hours at RT. The reaction mixture was worked up by adding 15 ml of saturated ammonium chloride solution while cooling in an ice bath and was extracted three times at RT, with 15 ml of ether each time. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 3.42 g of crude base (84.1% of theory) were obtained, from which a hydrochloride was precipitated according to Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone. The base was freed from the hydrochloride with 30 ml of water and 5 ml of ammonia solution (25 vol. %), extracted three times with 15 ml of ether each time, and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 2.89 g of crude base (78.6% of theory) were obtained, from which 2.58 g of 1-benzyl-2-[dimethylamino-(4-fluoro-phenyl)methyl]cyclohexanol, hydrochloride (63.3% of theory) having a melting point of 178° C. were obtained according to the procedure described in Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone.

Workup

  1. customobtained
  2. extractionextracted three times with 30 ml of ether each time
  3. dry with materialthe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated by evaporation on a rotary evaporator
  6. temperaturewithout heating (500 to 10 mbar)
  7. additionadded dropwise
  8. temperaturewhile cooling in an ice bath
  9. extractionwas extracted three times at RT
  10. dry with materialThe combined organic extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated by evaporation on a rotary evaporator (500 to 10 mbar)
  13. custom3.42 g of crude base (84.1% of theory) were obtained, from which a hydrochloride
  14. customwas precipitated
  15. extractionextracted three times with 15 ml of ether each time
  16. dry with materialthe combined organic extracts were dried over sodium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated by evaporation on a rotary evaporator (500 to 10 mbar)

Sources & evidence

ORD record
ord-295ff9bb52da497086c946c6d8d51884
Source dataset
uspto-grants-2002_06
Patent number
US06410790B1

Reaction notes

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