Ethyl Acetate → HCID 53241674, compound

HRID 1914912Notes

Reaction equation

HRID 1914912 reaction equation
B(Cl)(Cl)Cl.[F:5][C:6]1[C:11]2[CH:12]=[CH:13][O:14][C:10]=2[C:9]([NH:15][S:16]([CH:19]2[CH2:21][CH:20]2[CH2:22][O:23]CC2C=CC=CC=2)(=[O:18])=[O:17])=[C:8]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([I:38])=[CH:34][C:33]=2[F:39])[C:7]=1[F:40].C(OCC)(=O)C>C(Cl)Cl.CCCCCC>[F:5][C:6]1[C:11]2[CH:12]=[CH:13][O:14][C:10]=2[C:9]([NH:15][S:16]([CH:19]2[CH2:21][CH:20]2[CH2:22][OH:23])(=[O:17])=[O:18])=[C:8]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([I:38])=[CH:34][C:33]=2[F:39])[C:7]=1[F:40]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 25135Boron TrichlorideHCID 67237827HCID 67237827, compound

Product 1

HCID 53241674HCID 53241674, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-75 °C

Procedure

1M BCl3 solution in DCM (0.477 mL, 0.4777 mmol) was added dropwise to a solution of 2-benzyloxymethyl-cyclopropanesulfonic acid [4,5-difluoro-6-(2-fluoro-4-iodo-phenylamino)-benzofuran-7-yl]-amide (0.150 g, 0.2388 mmol) in dry DCM (5 mL) at −75° C. and stirred for 1 hour at −75° C. The reaction mass was allowed to attain 20-35° C. and continued the stirring for 2 hours at same temperature. The reaction was monitored by TLC (50% ethyl acetate in hexane). The reaction mass was quenched with saturated sodium bicarbonate solution and then diluted with DCM (50 mL). The organic layer was separated, washed with water, brine solution and concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (50% ethyl acetate in hexane) afforded 0.070 g of the product (55% yield). 1H NMR (DMSO-d6, 300 MHz): δ 9.38 (s, 1H), 8.19 (d, 1H), 7.77 (bs. 1H), 7.52 (dd, 1H), 7.33 (d, 1H), 7.22 (d, 1H), 6.42-6.44 (m, 1H), 4.53 (t, 1H), 3.21-3.31 (m, 1H), 3.02-3.10 (m, 1H), 1.41-1.46 (m, 1H), 1.20 (m, 1H) 0.85-0.90 (m, 1H), 0.75-0.79 (m, 1H). LCMS: 96.82%, m/z=536.9 (M−1). HPLC: 94.75%

Workup

  1. customto attain 20-35° C.
  2. customstirring for 2 hours
  3. customThe reaction mass was quenched with saturated sodium bicarbonate solution
  4. additiondiluted with DCM (50 mL)
  5. customThe organic layer was separated
  6. washwashed with water, brine solution
  7. concentrationconcentrated under reduced pressure
  8. customto afford the crude product
  9. customPurification by column chromatography on silica gel (50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-fc5d6f9f65c24c8ea2786ff800aa5f1d
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

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