Ethyl chloroformate → 7-Nitro-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester
Reaction equation
[N+:1]([C:4]1[CH:14]=[CH:13][C:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH2:12][C:6]=2[CH:5]=1)([O-:3])=[O:2].CCN(C(C)C)C(C)C.Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26]>C(Cl)Cl.Cl>[CH2:28]([O:27][C:25]([N:10]1[CH2:11][CH2:12][C:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:14]=[CH:13][C:7]=2[CH2:8][CH2:9]1)=[O:26])[CH3:29]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
To a stirred solution of the product from Example 36, step (a) (5 g, 26.0 mmol) dissolved in DCM (75 ml), DIEA (6.8 ml, 39 mmol) was added. The reaction mixture was cooled to 0° C. and ethyl chloroformate was added (3.0 ml, 31.2 mmol). The reaction mixture was stirred at 0° C. for 2 hours and then allowed to warm to room temperature. The reaction mixture was diluted with 2N HCl (150 ml) and extracted with DCM (3×). The combined DCM extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the crude product. Purification by silica-gel chromatography (gradient elution: 0 to 50% EtOAc in hexane) gave the sub-title compound as a light yellow solid (4.7 g). 1H NMR (300 MHz, DMSO-d6) δ 8.07 (d, J=2.4 Hz, 1H); 8.01 (dd, J=8.1 Hz, 2.4 Hz, 1H); 7.45 (d, J=8.1 Hz, 1H); 4.07 (q, J=6.9 Hz, 2H); 3.54-3.51 (m, 4H); 3.04-3.01 (m, 4H); 1.19 (t, J=7.2 Hz, 3H).
Workup
- temperatureto warm to room temperature
- extractionextracted with DCM (3×)
- washThe combined DCM extracts were washed with brine
- dry with materialdried over Na2SO4, and solvent
- customevaporated in vacuo
- customto give the crude product
- customPurification
- washby silica-gel chromatography (gradient elution: 0 to 50% EtOAc in hexane)
Sources & evidence
- ORD record
- ord-cbb657eccd994f81a6d8e52d8e970240
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09284277B2
Reaction notes
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