12
Journal of Fluorine Chemistry
4.16. (2,2-Difluorocyclopentyl)methyl acetate (31)
To a solution of DAST (156 g, 128 mL, 0.968 mol) in CH2Cl2 (650 mL), a solution of 29 (37.8 g, 0.242 mol) in CH2Cl2 (400 mL)
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was added at rt. The reaction mixture was refluxed for 72 h (monitored by H NMR), then cooled. Saturated aq NaHCO3 was added to
pH = 7. Aqueous layer was extracted with CH2Cl2 (2100 mL). The combined organic extracts were dried over Na2SO4 and evaporated
in vacuo. The residue was purified by column chromathography (hexanes –EtOAc (14 : 1) as eluent). Yield 20.5 g, 48%. Colourless oil.
Rf = 0.42 (hexanes –EtOAc (14 : 1)). 1H NMR (CDCl3, 400 MHz): = 4.21 (dd, J = 11.3, 7.1 Hz, 1H), 4.12 (dd, J = 11.3, 6.7 Hz, 1H),
2.56 – 2.39 (m, 1H), 2.24 – 1.93 (m, 3H), 2.06 (s, 3H), 1.88 – 1.66 (m, 2H), 1.59 – 1.48 (m, 1H). 13C NMR (CDCl3, 101 MHz): =
170.3, 131.1 (t, J = 251 Hz), 61.8 (d, J = 7.4 Hz), 44.7 (dd, J = 23.8, 21.4 Hz), 35.2 (t, J = 24.7 Hz), 26.5 (d, J = 5.8 Hz), 20.6, 20.1 (t, J
= 4.5 Hz). 19F NMR (CDCl3, 376 MHz): δ = –96.0 (ddd, J = 231, 25.7, 13.4 Hz), –107.0 (ddd, J = 231, 32.9, 16.0 Hz). MS (EI): m/z =
178 (M+), 98 (M+ – AcOH – HF), 86, 43 (CH3CO+). Anal. Calcd. for C8H12F2O2: C, 53.93; H, 6.79. Found: C, 53.72; H, 6.66.
4.17. (2,2-Difluorocyclohexyl)methyl acetate (32)
Compound 32 was prepared from compound 30 using the procedure described above for the compound 29. Yield 15.0 g, 45%.
Colorless oil. Rf = 0.38 (hexanes –EtOAc (14 : 1)). 1H NMR (400 MHz, CDCl3): δ = 4.38 (dd, J = 11.2, 5.1 Hz, 1H), 4.03 (dd, J = 11.2,
7.9 Hz, 1H), 2.17 – 2.02 (m, 2H), 2.06 (s, 3H), 1.94 – 1.82 (m, 1H), 1.82 – 1.44 (m, 4H), 1.42 – 1.20 (m, 2H). 13C NMR (101 MHz,
CDCl3): δ = 170.4, 123.0 (t, J = 244 Hz), 62.2 (t, J = 4.0 Hz), 42.7 (dd, J = 22.0, 19.7 Hz), 34.0 (dd, J = 24.7, 22.0 Hz), 26.3 (d, J = 6.5
Hz), 23.5, 22.4 (d, J = 9.1 Hz), 20.7. 19F NMR (CDCl3, 376 MHz): δ = –96.9 (d, J = 237 Hz), -114.1 (br d, J = 237 Hz). MS (EI): m/z =
172 (M+–HF), 112 (M+–AcOH–HF), 43 (CH3CO+). Anal. Calcd. for C9H14F2O2: C, 56.24; H, 7.34. Found: C, 56.25; H, 7.10.
4.18. (2,2-Difluorocyclopentyl)methanol (33)
Ester 31 (19.4 g, 0.109 mol) was dissolved in MeOH (200 mL), and NaOH (8.70 g, 0.218 mol) in H2O (20 mL) was added. The
reaction mixture was stirred at room temperature overnight. The solvent was evaporated, water (100 mL) was added, and the mixture
was extracted with CH2Cl2 (3100 mL). The organic layer was dried over Na2SO4 and evaporated in vacuo. Yield 12.1 g, 82%.
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Yellowish oil. H NMR (CDCl3, 400 MHz): = 3.80 (dd, J = 11.5, 7.1 Hz, 1H), 3.69 (dd, J = 11.5, 5.5 Hz, 1H), 2.45 – 2.27 (m, 1H),
2.22 – 1.91 (m, 3H), 1.83 (br s, 1H), 1.82 – 1.64 (m, 2H), 1.63 – 1.50 (m, 1H). 13C NMR (CDCl3, 101 MHz): = 132.5 (t, J = 251 Hz),
60.8 (d, J = 7.9 Hz), 47.7 (t, J = 21.7 Hz), 35.5 (t, J = 24.5 Hz), 25.9 (d, J = 5.0 Hz), 20.4. 19F NMR (CDCl3, 376 MHz): δ –93.4 (dq, J =
230, 14.0 Hz), –107.2 (dq, J = 230, 15.2 Hz). MS (EI): m/z = 136 (M+), 86 (M+–HF–CH2O). Anal. Calcd. for C6H10F2O: C, 52.93; H,
7.40. Found: C, 52.98; H, 7.12.
4.19. (2,2-Difluorocyclohexyl)methanol (34)
Compound 34 was prepared from compound 32 using the procedure described above for the compound 33. Used in the next step
without further purification. Yield 10.5 g, 90%. Yellowish oil. 1H NMR (400 MHz, CDCl3) δ 3.96 (dd, J = 11.4, 5.7 Hz, 1H), 3.62 (dd,
J = 11.4, 5.6 Hz, 1H), 2.16 – 2.02 (m, 1H), 2.02 – 1.82 (m, 2H), 1.82 – 1.45 (m, 5H), 1.34 (tt, J = 24.1, 12.2 Hz, 2H). 13C NMR (CDCl3,
101 MHz): = 124.5 (t, J = 243 Hz), 61.2 (t, J = 3.7 Hz), 45.7 (dd, J = 21.6, 18.7 Hz), 34.1 (dd, J = 24.9, 22.0 Hz), 25.9 (d, J = 7.0 Hz),