Ammonium Acetate → HCID 178451792, compound

HRID 419755Notes

Reaction equation

HRID 419755 reaction equation
C(OC(C1CC[N:11]([C:14](=O)[NH:15][CH2:16][C:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=2)=O)CC1)=O)(C)(C)C.[C:31]([O-:34])(=[O:33])C.[NH4+:35]>CO>[C:21]([O:34][C:31]([N:35]1[CH2:23][CH2:24][CH:19]([C:14]2[NH:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:27])([F:28])[F:29])[CH:20]=3)[N:11]=2)[CH2:17][CH2:16]1)=[O:33])([CH3:26])([CH3:22])[CH3:20]

Participants

4

Reactant 2

HCID 517165Ammonium AcetateHCID 666498871-[2-(4-Fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethylcarbamoyl]-piperidine-4-carboxylic acid tert-butyl ester

Product 1

HCID 178451792HCID 178451792, compoundYield 114.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
140 °C

Procedure

Combine 1-[2-(4-fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethylcarbamoyl]-piperidine-4-carboxylic acid tert-butyl ester (100 g, 231 mmoles), ammonium acetate (178.3 g; 2.31 moles, 10 eq), and methanol (1000 mL). The reactor used for this transformation is a coiled 1/16″ I.D. stainless steel tube (total internal volume of tubing in oven is 541 mol). Heat the reactor in an oven to 140° C. Control the back pressure in this tube at 250 psig by a regulator to allow super-heating of the solution above its normal boiling point. Pump the solution prepared above continuously through the heated tube under pressure at 6.01 mL/min (affording a total residence time in the heated tube of 90 minutes). As the solution exits the oven, cool it back to 20° C. in a tube-in-tube heat exchanger. Once the entire solution process through the reactor (8 hours total processing time), concentrate the resulting orange solution under vacuum at 30° C. to a total volume of 600 mL. Add acetonitrile (200 mL) and heat the solution to 50° C. Add water (700 mL) drop wise with seeding over 2 hours to crystallize the product. Cool the resulting slurry to 20° C. and filter the solid, then wash with 20% MeOH in water (2×200 mL). Dry the resulting solid under vacuum at 50° C. Re-slurry the solid in acetonitrile (200 mL) at 50° C. Cool the slurry to ambient temperature, filter the solid and wash with acetonitrile (100 mL) to afford 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (54.43 g, 132 mmoles, 57%) as an off white solid.

Workup

  1. temperatureControl the back pressure in this tube at 250 psig by a regulator to allow super-heating of the solution above its normal boiling point
  2. customprepared above continuously through the heated tube under pressure at 6.01 mL/min (
  3. customaffording a total residence time in the heated tube of 90 minutes)
  4. temperaturecool it back to 20° C. in a tube-in-tube
  5. temperatureheat exchanger
  6. concentrationOnce the entire solution process through the reactor (8 hours total processing time), concentrate the resulting orange solution under vacuum at 30° C. to a total volume of 600 mL
  7. temperatureAdd acetonitrile (200 mL) and heat the solution to 50° C
  8. customto crystallize the product
  9. temperatureCool the resulting slurry to 20° C.
  10. filtrationfilter the solid
  11. washwash with 20% MeOH in water (2×200 mL)
  12. customDry the resulting solid under vacuum at 50° C
  13. customat 50° C
  14. temperatureCool the slurry to ambient temperature
  15. filtrationfilter the solid
  16. washwash with acetonitrile (100 mL)

Sources & evidence

ORD record
ord-6f94912d95ab4d2395718f6a28f83457
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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