Acetyl chloride → N-(5-acetyl-6-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide

HRID 585805Notes

Reaction equation

HRID 585805 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[CH2:9]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[CH2:16][CH:15]([NH:20][C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])[CH2:14]2)[CH3:10].C(OC(C)C)(=O)C>Cl>[C:1]([C:19]1[CH:18]=[C:17]2[C:13](=[CH:12][C:11]=1[CH2:9][CH3:10])[CH2:14][CH:15]([NH:20][C:21](=[O:26])[C:22]([F:24])([F:23])[F:25])[CH2:16]2)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 7915Isopropyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 10171489N-(5-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide

Product 1

HCID 10236497N-(5-acetyl-6-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamideYield 94.4%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
0 °C

Procedure

A 250 mL, 4-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer, cooling bath, and nitrogen inlet-outlet, was charged with acetyl chloride (37.68 g, 480 mmol) and cooled to 0±5° C. Aluminum chloride (13.33 g, 100 mmol) was added in 4×3.33 g portions at 0±5° C. while maintaining the temperature below 15° C. The resulting solution was cooled to 0±5° C. and stirred for 5 minutes. N-(5-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (10.29 g, 40 mmol) was added in 5×2.06 g portions over 40 minutes at 10-minute intervals, while maintaining the temperature 0-10° C. The tan solution was stirred at 0±5° C. for an additional 30 minutes. The solution was added to a pre-cooled (0-5° C.) mixture of 1 N HCl (120 mL) and isopropyl acetate (13 mL) in a 500 mL, 3-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer, and a cooling bath, while maintaining the temperature at 0-25° C. over a period of 20 minutes. The 250 mL, round-bottomed flask was rinsed with 3 mL of acetyl chloride followed by 13 mL of heptane and added to the batch. The resulting slurry was warmed to 40-45° C. over a period of 30 minutes and then stirred for additional 1 hour. Heptane (39 mL) was added and the slurry was stirred at 40-45° C. for an additional 15 minutes. The slurry was cooled to 20-25° C. and stirred for 1 hour. The solids were collected by filtration using a Büchner funnel with suction over polypropylene filter paper. The filter cake was washed with 2×10 mL heptane/isopropyl acetate (80:20 v/v), followed by 1 N HCl (36 mL) and deionized water (2×25 mL). The solids were dried at 60-65° C. under vacuum (13-40 mbar, 10-30 torr) with nitrogen bleeding to obtain 11.3 g (94% yield) of N-(5-acetyl-6-ethyl-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (m.p. 124-127° C.).

Workup

  1. customA 250 mL, 4-necked, round-bottomed flask, equipped with a mechanical stirrer
  2. temperaturedigital thermometer, cooling bath, and nitrogen inlet-outlet
  3. temperaturewhile maintaining the temperature below 15° C
  4. temperatureThe resulting solution was cooled to 0±5° C.
  5. temperaturewhile maintaining the temperature 0-10° C
  6. stirringThe tan solution was stirred at 0±5° C. for an additional 30 minutes
  7. additionThe solution was added to
  8. temperaturea pre-cooled
  9. custom3-necked, round-bottomed flask, equipped with a mechanical stirrer
  10. temperaturedigital thermometer, and a cooling bath, while maintaining the temperature at 0-25° C. over a period of 20 minutes
  11. washThe 250 mL, round-bottomed flask was rinsed with 3 mL of acetyl chloride
  12. additionadded to the batch
  13. temperatureThe resulting slurry was warmed to 40-45° C. over a period of 30 minutes
  14. stirringstirred for additional 1 hour
  15. additionHeptane (39 mL) was added
  16. stirringthe slurry was stirred at 40-45° C. for an additional 15 minutes
  17. temperatureThe slurry was cooled to 20-25° C.
  18. stirringstirred for 1 hour
  19. filtrationThe solids were collected by filtration
  20. filtrationfilter paper
  21. washThe filter cake was washed with 2×10 mL heptane/isopropyl acetate (80:20 v/v)
  22. customThe solids were dried at 60-65° C. under vacuum (13-40 mbar, 10-30 torr) with nitrogen bleeding

Sources & evidence

ORD record
ord-78457604f60c44ed84035ca7990b62c9
Source dataset
uspto-grants-2005_08
Patent number
US06933410B2

Reaction notes

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