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

HRID 627973Notes

Reaction equation

HRID 627973 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

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 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).

Workup

  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

Sources & evidence

ORD record
ord-f0bcd42471a441b690819f6112e83f72
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

Loading…