tert-butyl N-(furan-2-yl)carbamate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl furan-2-ylcarbamate C3-2 (55.0 g, 300.2 mmol) and dimethyl but-2-ynedioate (73.5 mL, 600.4 mmol) in toluene (100 mL) was heated at 45° C. for 4 hrs. The solvent was removed in vacuo and the residue was purified by chromatography (silica gel, PE to EA:PE (1:20, v:v)) to give compound C3-2 as a light yellow solid (36.1 g, yield: 37%). 1H NMR (DMSO-d6, 400 MHz) δ: 1.41 (s, 9H), 3.69 (s, 3H), 3.73 (s, 3H), 7.02 (d, J=8.8 Hz, 1H), 7.35 (d, J=9.2 Hz, 1H), 8.93 (s, 1H), 10.07 (s, 1H); MS (ESI+): m/z 238 (M-87). The solvent was removed in vacuo the residue was purified by chromatography (silica gel, PE to EA:PE (1:20, v:v))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of furan-2-carboxylic acid (35.0 g, 312.2 mmol), triethylamine (86 mL, 624.5 mmol), and diphenyl phosphorazidate (DPPA) (135 mL, 624.5 mmol) in tert-butyl alcohol (400 mL) was refluxed overnight. The volatile was removed in vacuo and the residue was purified by chromatography (silica gel, PE to EA:PE (1:30, v:v)) to give compound C3-2 as a white solid (55.0 g, yield: 96%). 1H NMR (DMSO-d6, 400 MHz) δ: 1.43 (s, 9H), 5.91 (s, 1H), 6.37 (t, J=2.6 Hz, 1H), 7.26 (s, 1H), 9.81 (s, 1H). The volatile was removed in vacuo the residue was purified by chromatography (silica gel, PE to EA:PE (1:30, v:v))

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: reacting tert-butyl furan-2-ylcarbamate with dimethyl but-2-ynedioate via the Diels-Alder reaction to form dimethyl 3-(tert-butoxycarbonylamino)-6-hydroxyphthalate; via the Diels-Alder reaction

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyllithium in pentane (2.40 equiv) is added to a solution of tert-butyl 2-furylcarbamate (prepared by the method of Padwa, et al Org Synth 2000, 78, 2002, 1 equiv) in TEF at −78° C. The reaction mixture is stirred for 45 min, then solid CO2 (excess) is added and the resulting mixture is warmed to 0° C. and stirred for 30 minutes. The reaction mixture is partitioned between aqueous 1 N hydrochloric acid solution and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated. The residue is purified by flash column chromatography (hexanes initially, grading to 100% ethyl acetate), and the polar fractions are concentrated. A solution of the residue, benzylamine (2 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1 equiv), 1-hydroxy-7-azabenzotriazole (1 equiv), and triethylamine (2 equiv) in DMF is stirred at 55° C. for 24 h. The reaction mixture is concentrated, and the residue is partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated. The residue is purified by flash column (hexanes initially, grading to 100% ethyl acetate) to give tert-butyl 3-[(benzylamino)carbonyl]-2-furylcarbamate (1-1). prepared by the method of Padwa, et al Org Synth 2000, 78, 2002, 1 equiv) in TEF at −78° C stirred for 30 minutes The reaction mixture is partitioned between aqueous 1 N hydrochloric acid solution and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated The residue is purified by flash column chromatography (hexanes initially are concentrated The reaction mixture is concentrated the residue is partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated The residue is purified by flash column (hexanes initially