Ethyl Acetate → HCID 178518572, compound

HRID 1914896Notes

Reaction equation

HRID 1914896 reaction equation
[F:1][C:2]1[C:10]2[N:11]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:12](=[O:14])[NH:13][C:9]=2[C:8]2[O:7][CH:6]=[CH:5][C:4]=2[C:3]=1[F:23].[CH2:24]([O:31][CH2:32][CH:33]1[CH2:35][CH:34]1[S:36](Cl)(=[O:38])=[O:37])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(OCC)(=O)C>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCCCCC>[CH2:24]([O:31][CH2:32][CH:33]1[CH2:35][CH:34]1[S:36]([IH:21][C:18]1[CH:19]=[CH:20][C:15]([N:11]2[C:10]3[C:2]([F:1])=[C:3]([F:23])[C:4]4[CH:5]=[CH:6][O:7][C:8]=4[C:9]=3[NH:13][C:12]2=[O:14])=[C:16]([F:22])[CH:17]=1)(=[O:37])=[O:38])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 672379484,5-Difluoro-3-(2-fluoro-4-iodophenyl)-1H-benzofuro[6,7-d]imidazol-2(3H)-oneHCID 866563312-Benzyloxymethyl-cyclopropanesulfonyl chloride

Product 1

HCID 178518572HCID 178518572, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
30 °C

Procedure

TEA (0.0941 g, 0.930 mmol) was added to a solution of 4,5-difluoro-3-(2-fluoro-4-iodophenyl)-1H-1-benzofuro[6,7-d]imidazol-2(3H)-one (I-32a: 0.2 g, 0.4651 mmol) in dry DCM (5 mL) at 0° C. This was followed by the addition of 2-benzyloxymethyl-cyclopropanesulfonyl chloride (0.181 g, 0.6976 mmol) and catalytic amount of DMAP (0.010 g). The reaction mass was stirred for 12 hours at 20-40° C. The reaction was monitored by TLC (30% ethyl acetate in hexane). The reaction mass was diluted with DCM (50 mL) and partitioned between water and DCM. The organic layer was washed with water, brine solution and concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (15% ethyl acetate in hexane) afforded 0.180 g of the product (60% yield). 1H NMR (CDCl3, 300 MHz): δ 7.71 (d, 1H), 7.59-7.65 (m, 2H), 7.24-7.28 (m, 3H), 7.12-7.18 (m, 3H), 6.98 (d, 1H), 4.48 (s, 2H), 3.56 (dd, 1H), 3.38-3.48 (m, 1H), 3.25-3.35 (m, 1H), 2.28-2.38 (m, 1H), 1.56-1.58 (m, 1H), 1.38-1.48 (m, 1H). LCMS: 98.72%, m/z=654.9 (M+1)

Workup

  1. custompartitioned between water and DCM
  2. washThe organic layer was washed with water, brine solution
  3. concentrationconcentrated under reduced pressure
  4. customto afford the crude product
  5. customPurification by column chromatography on silica gel (15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f16d2e206efe4ddcb2c62af7e655e501
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

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