1,2-Dimethoxyethane → HCID 22458227, compound

HRID 2185567Notes

Reaction equation

HRID 2185567 reaction equation
CN(OC)[C:3](=[O:19])[CH2:4][CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([Mg]Br)=[CH:25][CH:24]=1.COCCOC.CCOC(C)=O>CCOCC>[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:3](=[O:19])[CH2:4][CH2:5][CH:6]2[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:10][CH2:11]2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 8857Ethyl AcetateHCID 22458230HCID 22458230, compoundHCID 178418676HCID 178418676, compound

Product 1

HCID 22458227HCID 22458227, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

N-Methyl-N-methoxy-3-(1-(tert-butoxycarbonyl)piperidin-4-yl)propionamide (550 mg, 1.83 mmol, from Step B) was dissolved in 10 mL dry ether and the solution was cooled to 0° C. A solution of 4-fluorophenyl magnesium bromide (2 mL, 1.0 M in THF, 2.01 mmol) was added dropwise. A solid mass formed upon addition and 1 mL 1,2-dimethoxyethane was added. The mixture was warmed to room temperature and stirred for 45 min then poured into 100 mL EtOAc/10 mL 1 M aqueous HCl. The layers were separated and the organic phase was washed with water, then sat'd NaCl, then dried over Na2SO4 and concentrated. Flash chromatography (25 grams silica, 5/1 hexane/EtOAc eluant) afforded 423 mg (69%) of the title compound. 1H NMR (300 MHz, CDCl3) δ1.0-1.20 (m, 2H), 1.45 (s, 9H), 1.65-1.75 (m 4H), 2.6-2.75 (m 2H), 2.9-3.0 (t, 2H), 4.03-4.08 (m, 2H), 7.1-7.19 (m, 2H), 7.95-8.04 (m, 2H).

Workup

  1. additionwas added
  2. temperatureThe mixture was warmed to room temperature
  3. customThe layers were separated
  4. washthe organic phase was washed with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-520bc885782c4463832b054746f8d8c1
Source dataset
uspto-grants-2002_06
Patent number
US06399619B1

Reaction notes

Loading…