3-{6-[(2,4-Dimethoxy-benzyl)-methyl-amino]-3H-isobenzofuran-1-ylidene}-1-hydroxymethyl-1,3-dihydro-indol-2-one → 1-hydroxymethyl-3-(6-methylamino-3H-isobenzofuran-1-ylidene)-1,3-dihydro-indol-2-one

HRID 1829018Notes

Reaction equation

HRID 1829018 reaction equation
COC1C=C(OC)C=CC=1[CH2:5][N:6](C)[C:7]1[CH:15]=[C:14]2[C:10]([CH2:11][O:12][C:13]2=[C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:25][OH:26])[C:17]2=[O:27])=[CH:9][CH:8]=1>C1COCC1.Cl>[OH:26][CH2:25][N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16](=[C:13]2[C:14]3[C:10](=[CH:9][CH:8]=[C:7]([NH:6][CH3:5])[CH:15]=3)[CH2:11][O:12]2)[C:17]1=[O:27]

Participants

4

Reactant 1

HCID 696592173-{6-[(2,4-Dimethoxy-benzyl)-methyl-amino]-3H-isobenzofuran-1-ylidene}-1-hydroxymethyl-1,3-dihydro-indol-2-one

Product 1

HCID 696593941-hydroxymethyl-3-(6-methylamino-3H-isobenzofuran-1-ylidene)-1,3-dihydro-indol-2-oneYield 6.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-{6-[(2,4-dimethoxy-benzyl)-methyl-amino]-3H-isobenzofuran-1-ylidene}-1-hydroxymethyl-1,3-dihydro-indol-2-one (600 mg, 1.31 mmol) in a mixture of THF (20 ml) and 2M HCl aqueous solution (20 ml) was heated at 50° C. for 16 hours. The mixture was concentrated, and then partitioned between CHCl3 (200 ml) and saturated NaHCO3 solution (200 ml). The aqueous layer was extracted with CHCl3 (2×100 ml). The combined organic layers were washed with water (100 ml), dried over anhydrous Na2SO4, and evaporated to give a dark brown oil as a crude product. Purification of the crude product by silica gel column chromatography, eluted with a gradient of MeOH in EtOAc, yielded 1-hydroxymethyl-3-(6-methylamino-3H-isobenzofuran-1-ylidene)-1,3-dihydro-indol-2-one as a yellow solid (25 mg, 6%).

Workup

  1. concentrationThe mixture was concentrated
  2. custompartitioned between CHCl3 (200 ml) and saturated NaHCO3 solution (200 ml)
  3. extractionThe aqueous layer was extracted with CHCl3 (2×100 ml)
  4. washThe combined organic layers were washed with water (100 ml)
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated
  7. customto give a dark brown oil as a crude product
  8. customPurification of the crude product by silica gel column chromatography
  9. washeluted with a gradient of MeOH in EtOAc

Sources & evidence

ORD record
ord-5cfa759e800840d2af9a930a19efac2b
Source dataset
uspto-grants-2006_06
Patent number
US07060844B2

Reaction notes

Loading…