N-methyl-2-pyrrolidone → HCID 24800928, compound

HRID 656520Notes

Reaction equation

HRID 656520 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]([O:10][CH2:11][C:12]2([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH3:9])[CH:5]=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=1.C[Si](C)(C)[C:37]([F:40])([F:39])[F:38].[F-].[K+].CN1CCCC1=O>CN(C)C=O.[Cu]I>[C:25]1([C:12]2([CH2:11][O:10][CH:8]([C:6]3[CH:5]=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=[C:2]([C:37]([F:40])([F:39])[F:38])[N:7]=3)[CH3:9])[CH2:13][CH2:14][NH:15][CH2:16][CH2:17]2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 522689Potassium FluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 57557584HCID 57557584, compound

Product 1

HCID 24800928HCID 24800928, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Tert-butyl 4-((1-(6-bromo-4-(trifluoromethyl)pyridin-2-yl)ethoxy)methyl)-4-phenylpiperidine-1-carboxylate (100 mg, 0.18 mmol), trimethyl(trifluoromethyl)silane (70 mg, 0.46 mmol), potassium fluoride (70 mg, 1.2 mmol) and Copper(I) Iodide (100 mg, 0.525 mmol) were combined in dry dimethylformamide (1 mL) and dry N-Methyl-2-pyrrolidinone (1 mL) in a sealed tube. The mixture was heated to 110° C. for 2 hours. After cooling the reaction mixture was quenched with the addition of ammonia hydroxide (6M, 15 mL). The reaction was diluted with ether, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting oil was redissolved in methanol (2 mL) and treated with HCl (g) for 30 seconds. The solvent was evaporated and preparatory HPLC afforded 14 mg (15%) of desired product as the TFA salt. 1H-NMR (CD3OD, 400 MHz) δ 7.92 (s, 1H), 7.24-7.57 (m, 6H), 4.54 (q, 1H), 3.91 (d, 1H), 3.57 (m, 1H), 2.82-3.03 (m, 2H), 2.51-2.77 (m, 2H), 2.34-2.48 (m, 2H), 2.03-2.22 (m, 2H), 1.38 (d, 3H). LC: Tr=1.785 min, HPLC Method 1. Mass spec.: 433.35 (MH)+.

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customwas quenched with the addition of ammonia hydroxide (6M, 15 mL)
  3. additionThe reaction was diluted with ether
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resulting oil was redissolved in methanol (2 mL)
  9. additiontreated with HCl (g) for 30 seconds
  10. customThe solvent was evaporated

Sources & evidence

ORD record
ord-310839db0f4f4ba587a6f6277c8597cd
Source dataset
uspto-grants-2011_12
Patent number
US08071778B2

Reaction notes

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