Dimethylformamide → 3-(2-Carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indan-2-ylacetic acid

HRID 650422Notes

Reaction equation

HRID 650422 reaction equation
[C:1]([CH2:8][O:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[CH:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH2:28][CH2:29][CH3:30])[CH:25]=2)[CH:20]([C:31]2[CH:36]=[CH:35][C:34]3[O:37][CH2:38][O:39][C:33]=3[CH:32]=2)[CH:19]1[CH2:40]C#N)([O:3]C(C)(C)C)=[O:2].C(CC1C(C2C=CC([O:61]C)=CC=2O)C2C(=CC=C(OCCC)C=2)C1C1C=CC2OCOC=2C=1)#N.[H-].[Na+].C(OC(=O)CBr)CCC.CN([CH:91]=[O:92])C>>[C:1]([CH2:8][O:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[CH:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH2:28][CH2:29][CH3:30])[CH:25]=2)[CH:20]([C:31]2[CH:36]=[CH:35][C:34]3[O:37][CH2:38][O:39][C:33]=3[CH:32]=2)[CH:19]1[CH2:40][C:91]([OH:92])=[O:61])([OH:3])=[O:2]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 87883Butyl bromoacetateHCID 867521292-Cyanomethyl-3-(2-hydroxy-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indaneHCID 1317204703-(2-Carbo-t-butoxymethoxy-4-methoxyphenyl)-2-cyanomethyl-1-(3,4-methylenedioxyphenyl)-5-propoxyindane

Product 1

HCID 101663713-(2-Carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indan-2-ylacetic acidYield 79%

Conditions

Temperature
0 °C

Procedure

1RS,2RS,3RS)-3-(2-Carbo-t-butoxymethoxy-4-methoxyphenyl)-2-cyanomethyl-1-(3,4methylenedioxyphenyl)-5-(prop-1-yloxy)indane. To a solution of 1RS,2RS,3RS)-2-cyanomethyl-3-(2-hydroxy-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane (250 mg, 0.55 mmol) in DMF (4 ml) stirred at 0° C. under argon added NaH (21 mg of 80% oil dispersion, 0.7 mmol). The mixture stirred at 0° C. for 15 min then t -butylbromoacetate (107 mg, 0.55 mmol) was added. The cooling bath was removed and the mixture was stirred for 3 h at room temperature then partitioned between EtOAc and 3N HCl. The organic extract was washed with H2O, saturated NaHCO3 solution, H2O, then brine, dried (Na2SO4) and solvent removed in vacuo. The residue was purified by flash chromatography on silica gel, (eluent 25-50% Et2O/hexanes) to afford the title compound as an oil (247 mg, 79%).

Workup

  1. additionwas added
  2. customThe cooling bath was removed
  3. stirringthe mixture was stirred for 3 h at room temperature
  4. customthen partitioned between EtOAc and 3N HCl
  5. extractionThe organic extract
  6. washwas washed with H2O, saturated NaHCO3 solution, H2O
  7. dry with materialbrine, dried (Na2SO4) and solvent
  8. customremoved in vacuo
  9. customThe residue was purified by flash chromatography on silica gel, (eluent 25-50% Et2O/hexanes)

Sources & evidence

ORD record
ord-5ff1755585c44a8686644585fe28b04a
Source dataset
uspto-grants-2001_08
Patent number
US06271399B1

Reaction notes

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