Trifluoroacetic acid → HCID 22915241, compound

HRID 1384387Notes

Reaction equation

HRID 1384387 reaction equation
CO[CH2:3][N:4]([CH2:12][Si](C)(C)C)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH2:17]([O:19][C:20](=[O:38])/[C:21](/[CH3:37])=[CH:22]/[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:24]=1)[CH3:18].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:17]([O:19][C:20]([C:21]1([CH3:37])[CH:22]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)[CH:24]=2)[CH2:3][N:4]([CH2:5][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:12]1)=[O:38])[CH3:18]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine2×HCID 10685933HCID 10685933, compound

Product 1

HCID 22915241HCID 22915241, compoundYield 61.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-methoxymethyl-N-(phenylmethyl)trimethylsilylmethylamine (27 g, 113.7 mmol) and (E)-3-(3-cyclopentyloxy-4-methoxyphenyl)-2-methyl-acrylic acid ethyl ester (19 g, 62.4 mmol) in CH2Cl2 (50 mL), cooled to 0° C., was added trifluoroacetic acid (1.0 M in CH2Cl2, 22.8 mL, 22.8 mmol). The reaction mixture was stirred at room temperature for 1 hour, then another molar equivalent of N-methoxymethyl-N-(phenylmethyl)tri-methylsilylmethylamine (14.8 g, 62.4 mmol) added over 10 minutes. Stirring was continued for 3 hours, then the CH2Cl2 was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with 1.0 N aqueous HCl (2×50 mL), water, 1.0 N aqueous NaOH solution, water, and brine, then dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a pale yellow oil. Chromatography on silica gel (9:1, hexanes:ethyl acetate) provided the product as an amber oil (16.7 g, 61% yield). 1H NMR (300 MHz, CDCl3) δ (ppm); 7.39-7.23 (m, 5H, aromatic), 6.91 (s, 1H, aromatic), 6.78 (m, 2H, aromatic), 4.75 (m, 1H), 4.18 (q, 2H, OEt), 3.86 (m, 1H), 3.81 (s, 3H, OCH3), 3.75 (d, 1H, J=13.2 Hz), 3.62 (d, 1H, J=13.2 Hz), 3.20 (d, 1H, J=9.5 Hz), 3.01 (m, 1H), 2.91 (m, 1H), 2.51 (d, 1H, J=9.5 Hz), 1.93-1.58 (M, 8H, cyclopentyl), 1.28 (t, 3H, OEt), 0.9 (s, 3H, CH3).

Workup

  1. stirringStirring
  2. waitwas continued for 3 hours
  3. customthe CH2Cl2 was removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with 1.0 N aqueous HCl (2×50 mL), water, 1.0 N aqueous NaOH solution, water, and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a pale yellow oil

Sources & evidence

ORD record
ord-d7c93f31d94540d795d4b664b569985c
Source dataset
uspto-grants-2001_07
Patent number
US06258833B1

Reaction notes

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