Butyric Acid → Methyl 4-[5-(2-carboxy-1-hydroxybutyl)-1-propylindol-3-ylmethyl]-3-methoxybenzoate

HRID 330206Notes

Reaction equation

HRID 330206 reaction equation
[C:1]([OH:6])(=[O:5])[CH2:2][CH2:3][CH3:4].C([N-]C(C)C)(C)C.[Li+].CN1C(=O)N(C)CCC1.[CH:24]([C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH2:35][CH2:36][CH3:37])[CH:30]=[C:29]2[CH2:38][C:39]1[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][C:40]=1[O:49][CH3:50])=[O:25].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[C:1]([CH:2]([CH2:3][CH3:4])[CH:24]([C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH2:35][CH2:36][CH3:37])[CH:30]=[C:29]2[CH2:38][C:39]1[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][C:40]=1[O:49][CH3:50])[OH:25])([OH:6])=[O:5]

Participants

7

Reactant 5

HCID 264Butyric Acid2×HCID 311Citric AcidHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 14882683Methyl 4-(5-formyl-1-propylindol-3-ylmethyl)-3-methoxybenzoate

Product 1

HCID 19870602Methyl 4-[5-(2-carboxy-1-hydroxybutyl)-1-propylindol-3-ylmethyl]-3-methoxybenzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the dianion of butyric acid (5.6 mmol) [prepared from butyric acid (5.6 mmol) and lithium di-isopropylamide (5.6 mmol) in tetrahydrofuran (THF) (30 ml) and dimethylpropyleneurea (11.2 mmol)]was added to a solution of methyl 4-[5-formyl-1-propylindol-3-ylmethyl]-3-methoxybenzoate (2.0 g) in THF (15 ml) cooled in an ice-bath, under a nitrogen atmosphere, at such a rate as to maintain the temperature of the reaction below 10°. The mixture was allowed to warm to room temperature, stirred for an additional hour, poured into 20% (w/v) citric acid solution (150 ml), and extracted with ethyl acetate. The organic extracts were washed (water (twice), brine), dried (MgSO4) and evaporated to give a yellow oil. The product was purified by flash chromatography, eluting with 80:20:2 toluene:ethyl acetate:acetic acid, to give methyl 4-[5-(2-carboxy-1-hydroxybutyl)-1-propylindol-3-ylmethyl]-3-methoxybenzoate (1.25 g, 48%, as a separable mixture of diastereomers), as a foam; isomer A partial NMR (300 Mz, DMSO-d6): 0.66(t, 3H, CH3), 0.81 (t, 3H, CH3), 3.83(s, 3H, OCH3), 3.92(s, 3H, OCH3), 4.53(d, 1H, CHOH), 5.23(br s, 1H, CHOH); isomer B partial NMR (300 Mz, DMSO-d6): 0.85(m, 6H, 2×CH3), 3.83(s, 3H, OCH3), 3.92(s, 3H, OCH3), 4.62(d, 1H, CHOH), 5.20(br s, about 1H, CHOH).

Workup

  1. temperaturecooled in an ice-bath, under a nitrogen atmosphere
  2. temperatureat such a rate as to maintain
  3. customthe temperature of the reaction below 10°
  4. extractionextracted with ethyl acetate
  5. washThe organic extracts were washed (water (twice), brine),
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customto give a yellow oil
  9. customThe product was purified by flash chromatography
  10. washeluting with 80:20:2 toluene

Sources & evidence

ORD record
ord-56e208c7ac034fe2b12c456f84428343
Source dataset
uspto-grants-1990_01
Patent number
US04894386

Reaction notes

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