Dimethylformamide → 7-Bromo-5-chloro-2,3-dihydro-benzo[b]oxepine-4-carbaldehyde

Reaction equation

[Br:1][C:2]1[CH:13]=[CH:12][C:5]2[O:6][CH2:7][CH2:8][CH2:9][C:10](=O)[C:4]=2[CH:3]=1.O=P(Cl)(Cl)[Cl:16].CN([CH:22]=[O:23])C>>[Br:1][C:2]1[CH:13]=[CH:12][C:5]2[O:6][CH2:7][CH2:8][C:9]([CH:22]=[O:23])=[C:10]([Cl:16])[C:4]=2[CH:3]=1

Participants

Reactant 3

HCID 6228Dimethylformamide

HCID 24813Phosphorus oxychloride

HCID 106815487-Bromo-3,4-dihydro-1-benzoxepin-5(2H)-one

Product 1

HCID 866348457-Bromo-5-chloro-2,3-dihydro-benzo[b]oxepine-4-carbaldehyde

Procedure

To a stirred solution of 7-bromo-3,4-dihydro-2H-benzo[b]oxepin-5-one (9.84 g; 41 mmol) in DMF (50 ml) at 0° C. was added POCl3 (10 ml; 107 mmol) dropwise over 10 min. The reaction mixture was stirred whilst allowing to warm to room temperature overnight (16 h) upon which time it was quenched by pouring into well-stirred ice/water (500 ml). The resulting solid was extracted into EtOAc (2×400 ml), the combined organics were dried (MgSO4) and concentrated to give a yellow solid (7-bromo-5-chloro-2,3-dihydro-benzo[b]oxepine-4-carbaldehyde). This solid was dissolved in DMF (50 ml) and treated successively with K2CO3 (7 g; 51 mmol) then ethyl mercaptoacetate (5.5 ml; 50 mmol). The reaction mixture was heated at 70° C. for 4 h upon which time it was cooled and poured into well-stirred ice/water (500 ml). The resulting solid was collected by filtration and dried to give 9-Bromo-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-2-carboxylic acid ethyl ester as an off-white solid (13.69 g; 95%). δH (400 MHz, d6-DMSO) 1.31 (t, J=7.2, 3H), 3.23 (t, J=5.2, 2H), 4.27-4.35 (m, 4H), 7.03 (d, J=8.8, 1H), 7.42 (dd, J=8.8 and 2.4, 1H), 7.70 (s, 1H), 7.80 (d, J=2.4, 1H).