Toluene → HCID 131728412, compound

HRID 1162847Notes

Reaction equation

HRID 1162847 reaction equation
[O:1]=[C:2]([CH2:6][CH3:7])[C:3](O)=O.[C:8]([O:12][C:13]([N:15]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)CC(N(OC)C)=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].C1(C)C=CC=CC=1.C([Mg]Br)=C.[CH3:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>C1COCC1.O>[C:8]([O:12][C:13](=[O:14])[N:15]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=1)[CH2:3][C:2](=[O:1])[CH2:6][CH2:7][N:46]1[CH2:47][CH2:48][N:43]([CH3:42])[CH2:44][CH2:45]1)([CH3:9])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 1140TolueneHCID 531671-MethylpiperazineHCID 131728413HCID 131728413, compoundHCID 178418507HCID 178418507, compound

Product 1

HCID 131728412HCID 131728412, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N2-tert-Butyloxycarbonyl-N2-(4-fluorobenzyl)-N1-methoxy-N1-methylglycinamide oxobutanoate (1.72 g, 5.28 mmol, from Example 6, Step 4) was azeotroped with anhydrous toluene (20 mL) and dissolved in anhydrous THF (53 mL). The solution was cooled to 0° C. and treated rapidly with vinylmagnesium bromide (866 mg, 6.60 mmol) under inert atmosphere. After stirring for 20 min at 0° C. and warming to ambient temperature over 40 min, the mixture was treated with N-methylpiperazine (585 μL, 5.28 mmol) and water (8 ml) and stirred for 20 min. The reaction was partitioned between EtOAc and brine, and the organic layer was washed twice with water, dried over Na2SO4, and concentrated in vacuo. The residue was azeotroped with CHCl3 to afford the title compound as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.26-7.17 (m, 3H), 7.03-7.00 (m, 1H), 4.45 (d, J=16.8 Hz, 2H), 3.93 (d, J=54.8 Hz, 2H), 2.67-2.45 (m, 12H), 2.27 (s, 3H), 1.46 (d, J=8.4 Hz, 9H). ES MS (M+1)=394.5.

Workup

  1. temperaturewarming to ambient temperature over 40 min
  2. stirringstirred for 20 min
  3. customThe reaction was partitioned between EtOAc and brine
  4. washthe organic layer was washed twice with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was azeotroped with CHCl3

Sources & evidence

ORD record
ord-f5ea17df0586488cbbcef58a2622ea7b
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

Loading…