Acetyl chloride → 1-(4,4-Dimethylthiochroman-6-yl)ethanone

HRID 1062837Notes

Reaction equation

HRID 1062837 reaction equation
[CH3:1][C:2]1([CH3:12])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[S:5][CH2:4][CH2:3]1.[Cl-].[Al+3].[Cl-].[Cl-].[C:17](Cl)(=[O:19])[CH3:18]>C(Cl)CCl>[CH3:1][C:2]1([CH3:12])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:17](=[O:19])[CH3:18])[CH:10]=2)[S:5][CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 110194304,4-Dimethylthiochroman

Product 1

HCID 117083551-(4,4-Dimethylthiochroman-6-yl)ethanone

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
-10 °C

Procedure

In a 5 L 4-neck round bottom flask, EDC (2 L) was added to the 4,4-dimethylthiochroman from the previous step. The contents were stirred and cooled to a temperature of about −10° C. Aluminum chloride (252 g) was slowly added to the reaction mixture. Acetyl chloride (152.7 g) was added at a temperature ranging from about −10° C. to about −5° C. over about 1.5 hours. After the addition, the reaction mixture was maintained at a temperature ranging from about −5° C. to about 0° C. for about 2 hours. The reaction was monitored by TLC. [If the reaction is incomplete as determined by TLC, bring the reaction mixture to a temperature ranging from about 25° C. to about 35° C. under stirring for about 4 hours.] The reaction mixture was quenched with ice (4.87 kg) and hydrochloric acid (1.63 L), and the reaction mass was stirred for about 30 minutes. EDC (2.5 L) was added to the reaction mass. The layers were separated. The aqueous layer was extracted with MDC (2×2 L). The organic layers were combined and washed with 5% sodium bicarbonate solution (2×2 L) and water (2×2 L) until the pH is about 7. This was followed by a washing with brine (1.5 L). The EDC and MDC layer were distilled out under reduced pressure until the moisture content was less than about 0.1%. There was a residual volume of about 3 L.

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was maintained at a temperature
  3. waitranging from about −5° C. to about 0° C. for about 2 hours
  4. customranging from about 25° C. to about 35° C.
  5. stirringunder stirring for about 4 hours
  6. custom] The reaction mixture was quenched with ice (4.87 kg) and hydrochloric acid (1.63 L)
  7. stirringthe reaction mass was stirred for about 30 minutes
  8. additionEDC (2.5 L) was added to the reaction mass
  9. customThe layers were separated
  10. extractionThe aqueous layer was extracted with MDC (2×2 L)
  11. washwashed with 5% sodium bicarbonate solution (2×2 L) and water (2×2 L) until the pH is about 7
  12. distillationThe EDC and MDC layer were distilled out under reduced pressure until the moisture content

Sources & evidence

ORD record
ord-834c6f9b9ed94fa0a9056dcf49d47853
Source dataset
uspto-grants-2005_11
Patent number
US06963002B2

Reaction notes

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