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

HRID 650423Notes

Reaction equation

HRID 650423 reaction equation
[C:1]([CH2:4][O:5][C:6]1[C:11](OC)=[CH:10][CH:9]=[CH:8][C:7]=1[CH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][CH2:25][CH3:26])[CH:21]=2)[CH:16]([C:27]2[CH:32]=[CH:31][C:30]3[O:33][CH2:34][O:35][C:29]=3[CH:28]=2)[CH:15]1[CH2:36][C:37]([OH:39])=[O:38])([OH:3])=[O:2].C1C2C(=CC=CC=2)CC1.[OH-:49].[Na+].O.[CH3:52]O>>[C:1]([CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:49][CH3:52])[CH:9]=[CH:8][C:7]=1[CH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][CH2:25][CH3:26])[CH:21]=2)[CH:16]([C:27]2[CH:32]=[CH:31][C:30]3[O:33][CH2:34][O:35][C:29]=3[CH:28]=2)[CH:15]1[CH2:36][C:37]([OH:39])=[O:38])([OH:3])=[O:2]

Participants

6

Reactant 5

HCID 887MethanolHCID 962WaterHCID 10326IndaneHCID 14798Sodium HydroxideHCID 70232555(1RS,2SR,3RS)-3-(2-Carboxymethoxy-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indan-2-ylacetic acid

Product 1

HCID 101663713-(2-Carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indan-2-ylacetic acidYield 90%

Conditions

Temperature
70 °C

Procedure

(1RS,2SR,3RS)-3-(2-Carboxymethoxy-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indan-2-ylacetic acid. To a solution of 1RS,2RS,3RS)-3-(2-carboxymethoxy-4-methoxyphenyl)-2-cyanomethyl-1-(3,4-methylenedioxyphenyl)-5-prop-1-yloxy)indane (290 mg, 0.56 mmol) in methanol (ca. 1 ml) was added aqueous 2 N NaOH solution (0.3 ml) followed by H2O (8 ml) then (with caution) Na2O2 (120 mg). The mixture was heated to 70° C. and stirred for 20 h at which time HPLC showed only 15% hydrolysis. The mixture was stirred at 85° C. for 3 days with 3 (100 mg) portions of Na22 added each day. the reaction mixture was partitioned between EtOAc and 3N HCl. The organic extract was washed with H2O then brine, dried (Na2SO4) and solvent removed in vacuo to afford the product as an oil (228 mg, 90% pure by HPLC) Final purification was obtained by crystallization as the bis cyclohexylamine salt. mp 210-212° C.

Workup

  1. custom15% hydrolysis
  2. additionadded each day
  3. customthe reaction mixture was partitioned between EtOAc and 3N HCl
  4. extractionThe organic extract
  5. washwas washed with H2O
  6. dry with materialbrine, dried (Na2SO4) and solvent
  7. customremoved in vacuo

Sources & evidence

ORD record
ord-d346557894a94b978056e3adf9f3385d
Source dataset
uspto-grants-2001_08
Patent number
US06271399B1

Reaction notes

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