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

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).

1. customwas quenched
2. additionby pouring
3. stirringinto well-stirred ice/water (500 ml)
4. extractionThe resulting solid was extracted into EtOAc (2 400 ml)
5. dry with materialthe combined organics were dried (MgSO4)
6. concentrationconcentrated

ORD record

ord-0dc08c6a64574faea01fb824ebbcaefa

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846762B2