Triethylamine → Ethyl 2-(4-(3-(2-(tert-butoxycarbonylamino)cyclohexyl)ureido)-2-chlorophenyl)acetate

To a solution of ethyl 2-(4-amino-2-chlorophenyl)acetate (178 mg, 0.833 mmol) in dry dichloromethane (5 mL), was added triethylamine (2.32 mL, 16.66 mmol) followed by triphosgene (247 mg, 0.833 mmol) solution in dichloromethane (1 mL). The reaction mixture was stirred at room temperature for 1 h. To this mixture was then added tert-butyl 2-aminocyclohexylcarbamate (357 mg, 1.67 mmol) in dichloromethane (1 mL). The reaction mixture was stirred at room temperature for 4 h and concentrated. The residue was dissolved in ethyl acetate and washed with water (2×20 mL), brine (10 mL), dried and concentrated. The crude product was purified by flash column chromatography to afford the desired product as a mixture of cis and trans diastereomers (220 mg, 0.485 mmol, 58%). 1H NMR: 1.23-1.28 (m, 6H), 1.38 (s, 9H), 1.70-1.73 (m, 2H), 2.01-2.08 (m, 2H), 3.29-3.32 (m, 1H), 3.53-3.58 (m, 1H), 3.68 (s, 2H), 4.11-4.19 (m, 2H), 5.01 (d, 1H, J=8.8 Hz), 5.57 (d, 1H, J=8 Hz), 7.13 (d, 1H, J=8.4 Hz), 7.20 (d, 1H, J=6.8 Hz), 7.41 (s, 1H), 7.46 (s, 1H).

1. stirringThe reaction mixture was stirred at room temperature for 4 h
2. concentrationconcentrated
3. dissolutionThe residue was dissolved in ethyl acetate
4. washwashed with water (2×20 mL), brine (10 mL)
5. customdried
6. concentrationconcentrated
7. customThe crude product was purified by flash column chromatography

ORD record

ord-45423655ff5b4e95a0d7ba40524bab19

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08722720B2