Triethylamine → HCID 86610909, compound

HRID 2377032Notes

Reaction equation

HRID 2377032 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[C@@H:10]([OH:20])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[F:28][C:29]([F:44])([F:43])[C:30]1[CH:31]=[C:32]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[C:33](Cl)=[O:34]>C(Cl)Cl>[F:28][C:29]([F:43])([F:44])[C:30]1[CH:31]=[C:32]([CH:36]=[C:37]([C:39]([F:42])([F:40])[F:41])[CH:38]=1)[C:33]([O:20][C@@H:10]1[C@@H:11]([C:13]2[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=2)[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1)=[O:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 56926702HCID 56926702, compound

Product 1

HCID 86610909HCID 86610909, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 250 mL 3-neck round bottom flask equipped with septa, magnetic stir bar thermocouple and nitrogen line was added 5.0 g (17.77 mmol) (3R,4S) tert-butyl-3-hydroxy-4-(4-fluorophenyl)pyrrolidine-1-carboxylate (Example 2, Step B, Rt 13.686 min) and 100 mL methylene chloride. To the resulting solution was added 5.0 mL (35.54 mmol) triethylamine by syringe. The reaction mixture was cooled to 0° C. and 3.80 mL (19.55 mmol) 3,5-bis(trifluoromethyl)benzoyl chloride was added slowly by syringe over 10 min. A white precipitate formed after the addition was complete and the resulting mixture stirred for 1 hr at 0° C. when the cooling bath was removed. The reaction mixture was stirred an additional 2 hr at which time TLC (EtOAc/hex; 3:7) showed no starting material remained. The reaction mixture was poured into a separatory funnel which contained sat. aq. NaHCO3. The layers were separated, the organic layer dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum to give the title compound as a yellow oil which was used without further purification in the next reaction. 1H-NMR (CDCl3): δ: 1.55 (s, 9H), 3.4-4.09 (br. m, 6H), 5.41 (s, 1H), 7.06 (m, 2H), 7.30 (m, 2H), 8.12 (s, 1H), 8.44 (s, 2H)ppm.

Workup

  1. customTo a 250 mL 3-neck round bottom flask equipped with septa, magnetic stir bar thermocouple and nitrogen line
  2. customA white precipitate formed
  3. additionafter the addition
  4. customwas removed
  5. stirringThe reaction mixture was stirred an additional 2 hr at which time TLC (EtOAc/hex; 3:7)
  6. additionThe reaction mixture was poured into a separatory funnel which
  7. customThe layers were separated
  8. dry with materialthe organic layer dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-f8b0aa8e59e243f9882bccda555800ad
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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