2-Methoxyphenylacetic acid → (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)-2-(2-methoxyphenylacetyl)perhydroisoindol-4-ol

HRID 1599144Notes

Reaction equation

HRID 1599144 reaction equation
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[OH:23][CH2:24][CH:25]1[CH2:33][CH:32]2[CH:28]([CH2:29][NH:30][CH2:31]2)[C:27]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[F:41])([OH:34])[CH2:26]1.[CH3:42][O:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[CH2:50][C:51](O)=[O:52]>ClCCl>[OH:23][CH2:24][CH:25]1[CH2:33][CH:32]2[CH:28]([CH2:29][N:30]([C:51](=[O:52])[CH2:50][C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=3[O:43][CH3:42])[CH2:31]2)[C:27]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[F:41])([OH:34])[CH2:26]1

Participants

6

Reactant 4

HCID 71342-Methoxyphenylacetic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67660518(3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)perhydroisoindol-4-ol

Product 1

HCID 67660448(3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)-2-(2-methoxyphenylacetyl)perhydroisoindol-4-olYield 57.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.066 g of 1-hydroxybenzotriazole and 1.15 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added to a solution, cooled to 0° C., of 1.48 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)perhydroisoindol-4-ol and 0.98 g of 2-methoxyphenylacetic acid in 20 cm3 of dichloromethane. The mixture is stirred at room temperature for 18 hours and then the organic phase is washed with 20 cm3 of water and subsequently with 20 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 2.8 cm, height 20 cm), eluting under a pressure of 0.5 bar of nitrogen with ethyl acetate and collecting fractions of 20 cm3. Fractions 27 to 50 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 1.33 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-fluorophenyl)-2-(2-methoxyphenylacetyl)perhydroisoindol-4-ol are obtained in the form of a thick white foam.

Workup

  1. washthe organic phase is washed with 20 cm3 of water and subsequently with 20 cm3 of saturated aqueous sodium chloride solution
  2. dry with materialdried over magnesium sulphate
  3. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  4. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 2.8 cm, height 20 cm)
  5. washeluting under a pressure of 0.5 bar of nitrogen with ethyl acetate
  6. customcollecting fractions of 20 cm3
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-45f5b68d5a884413a143044ae6ce3f48
Source dataset
uspto-grants-1998_04
Patent number
US05739351

Reaction notes

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