Ethyl Acetate → 8-Cyclopropanesulfonyl-4,5-difluoro-6-(2-fluoro-4-iodo-phenyl)-6,8-dihydro-imidazo[4',5':3,4]benzo[1,2-d]oxazol-7-one

HRID 1914881Notes

Reaction equation

HRID 1914881 reaction equation
[F:1][C:2]1[C:7]2[N:8]=[CH:9][O:10][C:6]=2[C:5]2[NH:11][C:12](=[O:22])[N:13]([C:14]3[CH:19]=[CH:18][C:17]([I:20])=[CH:16][C:15]=3[F:21])[C:4]=2[C:3]=1[F:23].[CH:24]1([S:27](Cl)(=[O:29])=[O:28])[CH2:26][CH2:25]1.C(OCC)(=O)C>CN(C1C=CN=CC=1)C.C(Cl)Cl.CCCCCC>[CH:24]1([S:27]([N:11]2[C:5]3[C:6]4[O:10][CH:9]=[N:8][C:7]=4[C:2]([F:1])=[C:3]([F:23])[C:4]=3[N:13]([C:14]3[CH:19]=[CH:18][C:17]([I:20])=[CH:16][C:15]=3[F:21])[C:12]2=[O:22])(=[O:29])=[O:28])[CH2:26][CH2:25]1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 2760919Cyclopropanesulfonyl chlorideHCID 67253227HCID 67253227, compound

Product 1

HCID 672370348-Cyclopropanesulfonyl-4,5-difluoro-6-(2-fluoro-4-iodo-phenyl)-6,8-dihydro-imidazo[4',5':3,4]benzo[1,2-d]oxazol-7-oneYield 68.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

TEA (78 mg, 0.55 mmol) and DMAP (10 mg) were added to a solution of 4,5-difluoro-6-(2-fluoro-4-iodo-phenyl)-6,8-dihydro-imidazo[4′,5′:3,4]benzo[1,2-d]oxazol-7-one (I-15a: 80 mg, 0.178 mmol) in dry DCM (5 mL) at 0° C. and the resulting mixture was stirred for 15 minutes. This was followed by the addition of cyclopropanesulfonyl chloride (39 mg, 0.27 mmol) and stirring was continued for a further 3 hours at room temperature. The reaction was monitored by TLC (50% ethyl acetate in hexane). The reaction mixture was partitioned between water (50 mL) and ethyl acetate (50 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated to afford the crude product. Purification by column chromatography on silica gel (20-30% ethyl acetate in hexane) afforded 65 mg of the product (65% yield). H1NMR (CDCl3, 300 MHz): δ 8.14 (s, 1H), 7.72-7.65 (m, 2H), 7.28-7.24 (m, 1H), 3.35-3.25 (m, 1H), 1.75-1.60 (m, 2H), 1.35-1.25 (m, 2H).

Workup

  1. stirringstirring
  2. waitwas continued for a further 3 hours at room temperature
  3. customThe reaction mixture was partitioned between water (50 mL) and ethyl acetate (50 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto afford the crude product
  8. customPurification by column chromatography on silica gel (20-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-b03a0644f90148ca87195563ccd27d66
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

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