Dichloromethane → 3,3-Difluoro-1-((2-methoxy-4-nitrophenoxy)methyl)cyclobutanol

Participants

Reaction Steps

A mixture of 5,5-difluoro-1-oxaspiro[2.3]hexane+3 eq. CH2Cl2 (22.52 g, 0.06 mol), potassium 2-methoxy-4-nitrophenolate (12.43 g, 0.060 mol) prepared in Part E and NaH2PO4.H2O (7.45 g, 0.054 mol) in 50 mL MeCN-water (85:15) was heated at 130° C. in a steel bomb for 3.5 h. The reaction mixture was diluted with EtOAc, washed with 5% Na2CO3, dried (MgSO4) and concentrated. The crude product was recrystallized from ca. 150 mL MTBE giving 3,3-difluoro-1-((2-methoxy-4-nitrophenoxy)methyl)cyclobutanol (11.2 g, 0.039 mol, 64.5% yield) as a light yellow solid. An additional 1.2 g of a slightly less pure desired product was obtained upon concentration of the mother liquor to ca. 50 mL. 1H NMR (400 MHz, CDCl3) δ ppm 7.89 (1H, dd, J=8.94, 2.64 Hz), 7.76 (1H, d, J=2.77 Hz), 6.95 (1H, d, J=9.06 Hz), 4.16 (2 H, s), 3.94 (3 H, s), 3.36 (1H, s), 2.73-2.92 (4 H, m).

Provenance & Evidence