Benzyl (3-{2-[methoxy(methyl)amino]-2-oxoethyl}phenyl)carbamate → Benzyl [3-(2-oxobut-3-en-1-yl)phenyl]carbamate

HRID 243645Notes

Reaction equation

HRID 243645 reaction equation
CON(C)[C:4](=[O:23])[CH2:5][C:6]1[CH:7]=[C:8]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:9]=[CH:10][CH:11]=1.[CH:25]([Mg]Br)=[CH2:26]>C1COCC1>[O:23]=[C:4]([CH:25]=[CH2:26])[CH2:5][C:6]1[CH:7]=[C:8]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:9]=[CH:10][CH:11]=1

Participants

4

Reactant 2

HCID 57907449Benzyl (3-{2-[methoxy(methyl)amino]-2-oxoethyl}phenyl)carbamateHCID 178418507HCID 178418507, compound

Product 1

HCID 57907612Benzyl [3-(2-oxobut-3-en-1-yl)phenyl]carbamateYield 81.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 15 g (45.7 mmol) of benzyl (3-{2-[methoxy(methyl)amino]-2-oxoethyl}phenyl)carbamate (from Step C) in 1000 mL anhydrous THF under nitrogen atmosphere cooled to 0° C. via ice/water bath was added dropwise via cannula a 1.0 M solution of vinyl magnesium bromide (100 mL in THF, 100 mmol) and the resulting solution stirred for 1 h at 0° C. The reaction was quenched by a slow addition of 500 mL 1 M HCl keeping the temperature below 5° C. and stirred for 30 min. The mixture was then extracted with ethyl acetate and the combined organics washed with water followed by brine. The organics were then dried over sodium sulfate, filtered, and concentrate under vacuum. The residue was purified by Biotage 75M flash eluting with 30% ethyl acetate in hexane to afford the title compound (11 g, 78%) as a light yellow solid. LC-MS: m/z (ES) 310 (MH)+, 332 (MNa)+. 1HNMR (500 MHz, CDCl3) δ: 7.44-7.36 (m, 7H), 7.18 (d, J=8.4 Hz, 2H), 6.70 (br s, 1H), 6.44 (dd, J=10.5, 17.6 Hz, 1H), 6.32 (dd, J=1.1, 17.6 Hz, 1H), 5.85 (dd, J=1.1, 10.5 Hz, 1H), 5.22 (s, 2H), 3.86 (s, 2H).

Workup

  1. customThe reaction was quenched by a slow addition of 500 mL 1 M HCl keeping the temperature below 5° C.
  2. stirringstirred for 30 min
  3. extractionThe mixture was then extracted with ethyl acetate
  4. washthe combined organics washed with water
  5. dry with materialThe organics were then dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrate under vacuum
  8. customThe residue was purified by Biotage 75M flash
  9. washeluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-36c34bb674d548e2a942fa3134eb027a
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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