Dimethylformamide → HCID 57988827, compound

HRID 406915Notes

Reaction equation

HRID 406915 reaction equation
O.[K].[N+:3]([C:6]1[CH:7]=[C:8]([OH:14])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)([O-:5])=[O:4].BrC[C:17]([CH:19]1[CH2:21][CH2:20]1)=[O:18].[CH3:22]N(C=O)C>O>[CH:19]1([C:17](=[O:18])[CH2:13][O:12][C:9]2[CH:10]=[CH:11][C:6]([N+:3]([O-:5])=[O:4])=[CH:7][C:8]=2[O:14][CH3:22])[CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 109208412-Bromo-1-cyclopropylethan-1-oneHCID 1317257234-Nitroguaiacol potassium salt monohydrate

Product 1

HCID 57988827HCID 57988827, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

An orange suspension of 4-nitroguaiacol potassium salt hydrate (31.7 g, 153 mmol) and 2-bromo-1-cyclopropylethanone (29.4 g, 180 mmol), prepared in Example 48A, in DMF (310 mL) was heated at 80° C. for 1 h. LC-MS analysis revealed the conversion to product was complete. The resulting yellow reaction mixture was diluted with water (932 ml) and stirred for 4 hr as the mixture cooled to 20° C. Subsequent filtration yielded a yellow filter cake which after washing 3× with 150 mL of H2O and air drying yielded 34.6 g of 1-cyclopropyl-2-(2-methoxy-4-nitrophenoxy)ethanone as a light yellow solid. M.P. 112-113° C. 1H NMR (400 MHz, CDCl3): 6 ppm 0.95-1.03 (m, 2H), 1.13-1.18 (m, 2H), 2.15-2.23 (m, 1H), 3.95 (s, 3H), 4.86 (s, 2H), 6.73 (d, J=8.7 Hz, 1H), 7.75 (d, J=2.7 Hz, 1H), 7.82 (dd, J=8.7, 2.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ ppm 205.2, 152.7, 149.1, 117.3, 111.6, 106.9, 73.5, 56.3, 17.1, 12.0. HPLC: 5.8 min retention time, 98.7% API; ZORBAX® column SB C18 4.6×75 mm; flow rate 2.5 ml/min; Gradient solvent system: from 100% A:0% B to 0% A:100% B for 8 min (Solvent A: 10% MeOH-90% H2O=0.2% H3PO4; Solvent B: 90% MeOH-10% H2O+0.2% H3PO4) Detection at 220 nm. LC/MS: m/e 252.3 (M+H); 4 min gradient; 2.35 min retention.

Workup

  1. temperaturecooled to 20° C
  2. filtrationSubsequent filtration
  3. customyielded a yellow filter cake which
  4. washafter washing 3× with 150 mL of H2O and air
  5. customdrying

Sources & evidence

ORD record
ord-ef165e1fe3854c50a1eed17c352ff6bd
Source dataset
uspto-grants-2014_06
Patent number
US08754211B2

Reaction notes

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