Triethylamine → (R)-3-Bromo-2-hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide

HRID 2427844Notes

Reaction equation

HRID 2427844 reaction equation
[Br:1][CH2:2][C@@:3]([OH:8])([CH3:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[N+:13]([C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[C:23]([F:26])([F:25])[F:24])([O-:15])=[O:14].C(N(CC)CC)C>C1COCC1>[N+:13]([C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:4](=[O:5])[C@:3]([OH:8])([CH3:7])[CH2:2][Br:1])=[CH:18][C:17]=1[C:23]([F:24])([F:25])[F:26])([O-:15])=[O:14]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 949554-Nitro-3-(trifluoromethyl)anilineHCID 10582468(2R)-3-bromo-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 5287785(R)-3-Bromo-2-hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

A 50 L flask was set up with a mechanical stirrer, inlet for inert atmosphere, and cooling capacity. The flask was placed under an argon atmosphere and was charged with 2961.5 g (16.2 moles) of R-131 and 9.0 L of THF. The flask was cooled on ice to less than 5° C. Thionyl chloride (1200 mL, 16.4 moles) dissolved in 6.0 L of THF was added slowly via an addition funnel to the reaction flask. The temperature of the reaction flask was maintained less than or equal to 10° C. The addition time was 1 hour 10 minutes. The reaction mixture was allowed to agitate for an additional 2 hours 50 minutes. Then a solution of 2359.4 g of (11.4 moles) of 4-nitro-3-trifluoromethylaniline (Aldrich, 98%) and 3.83 L of triethylamine in 6.0 L THF was added over a period of 3 hours 5 minutes. The temperature of the reaction flask was maintained less than or equal to 10° C. The ice bath was removed, and the reaction mixture was allowed to stir for 30 minutes. With a heating mantle, the reaction mixture was heated to 50° C. for 15 hours and 10 minutes. After the reaction was complete as analyzed by TLC, the reaction mixture was cooled to less than 30° C. and 7.5 L of deionized water was added. The aqueous layer was removed and a second water wash (7.5 L) was performed. The organic layer was then washed three times with 10% bicarbonate (8.1 L) until the pH was greater than 7.

Workup

  1. customA 50 L flask was set up with a mechanical stirrer, inlet for inert atmosphere
  2. temperaturecooling capacity
  3. temperatureThe flask was cooled on ice to less than 5° C
  4. additionwas added slowly via an addition funnel to the reaction flask
  5. temperatureThe temperature of the reaction flask was maintained less than or equal to 10° C
  6. temperatureThe temperature of the reaction flask was maintained less than or equal to 10° C
  7. customThe ice bath was removed
  8. stirringto stir for 30 minutes
  9. temperaturethe reaction mixture was cooled to less than 30° C.
  10. addition7.5 L of deionized water was added
  11. customThe aqueous layer was removed
  12. washa second water wash (7.5 L)
  13. washThe organic layer was then washed three times with 10% bicarbonate (8.1 L) until the pH was greater than 7

Sources & evidence

ORD record
ord-0ecd05b782594c549b40938374038c63
Source dataset
uspto-grants-2011_06
Patent number
US07968721B2

Reaction notes

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