tert-Butanol → HCID 58218775, compound

HRID 1020994Notes

Reaction equation

HRID 1020994 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][CH:11]([C:15]([OH:17])=[O:16])[CH2:10]1.[C:18](O)([CH3:21])([CH3:20])[CH3:19].ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][CH:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]1

Participants

6

Reactant 3

HCID 6386tert-ButanolHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 47390401-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxylic acid

Product 1

HCID 58218775HCID 58218775, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a 2 L, 3-neck flask was added 1-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxylic acid (93 g, 0.40 mol), anhydrous tert-butanol (60 mL, 0.63 mol), TEA (110 mL, 0.79 mol), DMAP (5.0 g, 41 mmol), and CH2Cl2 (800 mL). After the mixture was cooled in an ice bath under nitrogen atmosphere with mechanical stirring, 2,4,6-trichlorobenzoyl chloride (108 g, 0.443 mol) was added in portions over the course of 15 minutes such that the temperature did not exceed 10° C. After the addition was complete, the ice bath was removed, the mixture was allowed to warm to room temperature and stirred for an additional 14 h. TLC and LCMS indicated complete consumption of starting material and formation of desired product. The mixture was filtered and the filter cake was washed with EtOAc (100 mL) and ether (150 mL). The filtrate was washed with two 200 mL portions of 1 M NaHSO4, four 200 mL portions of saturated aqueous NaHCO3, and brine (100 mL). After drying over MgSO4, the organic phase was treated with 24 g of silica gel, and filtered. The filtrate was concentrated to 250 mL and diluted with hexane. A crystalline precipitate began to form, and an initial crop of 66 g was recovered. The filtrate was recovered and recrystallized (ether/hexanes) to afford a second crop (27 g); overall yield, 93 g (81%). LC-MS Rt (retention time): 2.28 min, MS: (ES) m/z 290 (M+H+).

Workup

  1. additionwas added in portions over the course of 15 minutes such that the temperature
  2. customdid not exceed 10° C
  3. additionAfter the addition
  4. customthe ice bath was removed
  5. customconsumption of starting material and formation of desired product
  6. filtrationThe mixture was filtered
  7. washthe filter cake was washed with EtOAc (100 mL) and ether (150 mL)
  8. washThe filtrate was washed with two 200 mL portions of 1 M NaHSO4, four 200 mL portions of saturated aqueous NaHCO3, and brine (100 mL)
  9. dry with materialAfter drying over MgSO4
  10. additionthe organic phase was treated with 24 g of silica gel
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated to 250 mL
  13. additiondiluted with hexane
  14. customto form
  15. customan initial crop of 66 g was recovered
  16. customThe filtrate was recovered
  17. customrecrystallized (ether/hexanes)
  18. customto afford a second crop (27 g)
  19. custom2.28 min, MS

Sources & evidence

ORD record
ord-94c149d348114549b5753a7ef4b3dcf6
Source dataset
uspto-grants-2014_05
Patent number
US08716494B2

Reaction notes

Loading…