Pyridine → (3-Amino-4-tert-butyl-phenyl)-carbamic acid benzyl ester

HRID 74029Notes

Reaction equation

[C:1]([C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][C:6]=1[NH2:12])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.Cl[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21]>C(Cl)Cl.CO.C(Cl)Cl>[CH2:23]([O:22][C:20](=[O:21])[NH:11][C:8]1[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[C:6]([NH2:12])[CH:7]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 4-tert-butylbenzene-1,3-diamine (D-9) (657 mg, 4 mmol) and pyridine (0.39 mL, 4.8 mmol) in CH2Cl2/MeOH (12/1, 8 mL) was cooled to 0° C., and a solution of benzyl chloroformate (0.51 mL, 3.6 mmol) in CH2Cl2 (8 mL) was added dropwise over 10 min. The mixture was stirred at 0° C. for 15 min, then warmed to room temperature. After 1 h, the mixture was washed with 1M citric acid (2×20 mL), saturated aqueous sodium bicarbonate (20 mL), dried (Na2SO4), filtered and concentrated in vacuo to afford the crude (3-amino-4-tert-butyl-phenyl)-carbamic acid benzyl ester as a brown viscous gum (0.97 g), which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 7.41-7.32 (m, 6H), 7.12 (d, J=8.5 Hz, 1H), 6.89 (br s, 1H), 6.57 (dd, J=2.3, 8.5 Hz, 1H), 5.17 (s, 2H), 3.85 (br s, 2H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3, rotameric) δ 153.3 (br), 145.3, 136.56, 136.18, 129.2, 128.73, 128.59, 128.29, 128.25, 127.14, 108.63 (br), 107.61 (br), 66.86, 33.9, 29.7; ESI-MS 299.1 m/z (MH+).

Workup

temperaturewarmed to room temperature
waitAfter 1 h
washthe mixture was washed with 1M citric acid (2×20 mL), saturated aqueous sodium bicarbonate (20 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-cea542c3dff94cea99c1edc93518b40a
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829204B2

Reaction notes

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