Diethyl Ether → HCID 56670277, compound

HRID 1715325Notes

Reaction equation

HRID 1715325 reaction equation
COC1C=C(OC)C=CC=1C[N:6]1[CH2:10][C:9]([CH3:12])([CH3:11])[CH:8]([O:13][C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[C:16]([C:22]([F:25])([F:24])[F:23])[CH:15]=2)[C:7]1=[O:26].C([SiH](CC)CC)C.C(OCC)C>FC(F)(F)C(O)=O.ClCCl>[CH3:11][C:9]1([CH3:12])[CH2:10][NH:6][C:7](=[O:26])[CH:8]1[O:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[C:16]([C:22]([F:24])([F:23])[F:25])[CH:15]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 12052TriethylsilaneHCID 68505640HCID 68505640, compound

Product 1

HCID 56670277HCID 56670277, compoundYield 87.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 4-[1-(2,4-dimethoxy-benzyl)-4,4-dimethyl-2-oxo-pyrrolidin-3-yloxy]-2-trifluoromethyl-benzonitrile (25 g; 56 mmol) in trifluoroacetic acid (250 mL)and triethylsilane (20 g; 169 mmol; 3 eq) was brought to gentle reflux overnight. The reaction was cooled to ambient temperature. The reaction mixture was concentrated in vacuo to give an oily residue. The crude product was dissolved in dichloromethane and was washed with saturated aqueous sodium bicarbonate and with brine solution. The organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo to give a dark purple oily residue. The product was purified by flash silica column chromatography. Elution with a gradient (100% hexanes to 3:2 v/v ethyl acetate-hexanes over 1 hour, 12 minutes; pump speed: 1 mL/min) afforded an off-white powder. Trituration with diethyl ether over a steam bath afforded 14.6 g of a white powder; 1H-NMR (400 MHz; CDCl3) δ 7.75 (dd, 1H, J=8.6, 0.4 Hz), 7.46 (d, 1H, J=2.5 Hz), 7.37 (dd, 1H, J=8.6, 2.5 Hz), 6.46 (s, 1H), 4.53 (s, 1H), 3.21 (s, 1H), 3.20 (s, 1H), 1.27 (s, 3H), 1.25 (s, 3H); 19F-NMR (376 MHz; CDCl3) δ −62.66 (s, 3F); MS (APCl+) 299.1 (M+1, 100); (APCl−) 186.0 (100)

Workup

  1. temperatureto gentle reflux overnight
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto give an oily residue
  4. washwas washed with saturated aqueous sodium bicarbonate and with brine solution
  5. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a dark purple oily residue
  8. customThe product was purified by flash silica column chromatography
  9. washElution with a gradient (100% hexanes to 3:2 v/v ethyl acetate-hexanes over 1 hour, 12 minutes; pump speed: 1 mL/min)
  10. customafforded an off-white powder

Sources & evidence

ORD record
ord-1543155c46d0439caa21a005b6a622ae
Source dataset
uspto-grants-2010_09
Patent number
US07799823B2

Reaction notes

Loading…