tert-butyl 2-fluoro-4-hydroxyphenylcarbamate Chemical Properties

Melting point:

147-149 °C

Boiling point:

285.1±30.0 °C(Predicted)

Density 

1.254±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

9.18±0.31(Predicted)

Appearance

White to off-white Solid

tert-butyl 2-fluoro-4-hydroxyphenylcarbamate Usage And Synthesis

Synthesis

GENERAL STEPS: Synthesis of 4-(Boc-amino)-3-fluoro-phenol Method B: 4-amino-3-fluoro-phenol (10.61 g, 83.5 mmol) was added to a molten mixture of di-tert-butyl dicarbonate (Boc2O, 18.29 g, 83.8 mmol) and indium chloride (InCl3, 188 mg, 0.85 mmol), and reacted at a temperature of 35 °C. The reaction mixture was stirred at 35 °C for 2 h, during which it gradually transformed into a thick black oil. Subsequently, the mixture was diluted with ethyl acetate (EtOAc, 200 mL) and water (H2O, 200 mL) and stirring was continued for 10 min. The organic and aqueous layers were separated, the organic layer was washed with water (3 x 200 mL), dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated to dryness. The resulting black oil was redissolved in dichloromethane (CH2Cl2, 50 mL) and purified by silica gel column chromatography using a dichloromethane solution of 5→7% ethyl acetate as eluent to give 4-(Boc-amino)-3-fluoro-phenol as a light yellow crystalline solid. Yield: 16.7 g (90%). 1H-NMR (DMSO-d6), δ (ppm), J (Hz): 1.46 (s, 9H, tert-butyl), 6.08 (d, 1H, J = 5.5, HPy), 7.01 (m, 1H, aromatic hydrogen), 7.18 (br s, 2H, NH2), 7.22 (m, 1H, aromatic hydrogen), 7.67 (m, 1H, aromatic hydrogen). 8.04 (d, 1H, J = 5.5, p-H), 9.03 (s, 1H, NHBoc); 13C-NMR (DMSO-d6), δ (ppm), J (Hz): 28.0, 78.6, 102.7d (JFC = 22.2), 110.8 (d, JFC = 2.7), 117.1 (d, JFC = 12.6) 127.2, 153.7, 155.5 (d, JFC = 11.3), 156.1 (d, JFC = 246); 19F-NMR (DMSO-d6), δ (ppm): -121.6; LC-MS (m/z): 172.0 (M + H, 100).

References

[1] Journal of Medicinal Chemistry, 2009, vol. 52, # 13, p. 3881 - 3891
[2] Patent: WO2009/77766, 2009, A1. Location in patent: Page/Page column 95-96
[3] Patent: WO2011/92469, 2011, A1. Location in patent: Page/Page column 34-35
[4] Patent: CN108610284, 2018, A. Location in patent: Paragraph 0054; 0081
[5] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 19, p. 6525 - 6538