2-Methoxyphenylacetic acid → (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]perhydroisoindol-4-ol

HRID 1599158Notes

Reaction equation

HRID 1599158 reaction equation
Cl.CN(C)CCCN=C=NCC.[OH:13][CH2:14][CH:15]1[CH2:23][CH:22]2[CH:18]([CH2:19][NH:20][CH2:21]2)[C:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])([OH:24])[CH2:16]1.[CH3:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[CH2:41][C:42](O)=[O:43]>ClCCl>[OH:13][CH2:14][CH:15]1[CH2:23][CH:22]2[CH:18]([CH2:19][N:20]([C:42](=[O:43])[CH2:41][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[O:34][CH3:33])[CH2:21]2)[C:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])([OH:24])[CH2:16]1

Participants

5

Reactant 3

HCID 71342-Methoxyphenylacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67660910(3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-methoxyphenyl)perhydroisoindol-4-ol

Product 1

HCID 67714143(3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]perhydroisoindol-4-olYield 45.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

2.3 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added to a solution of 3 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-methoxyphenyl)perhydroisoindol-4-ol and 1.8 g of (2-methoxyphenyl)acetic acid in 60 cm3 of dichloromethane. The reaction mixture is stirred at 20° C. for 20 hours and then washed with 30 cm3 of water, 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 0.06-0.20 mm, height [lacuna]cm) in ethyl acetate and then in a mixture of ethyl acetate and methanol (95:5 by volume). Drying under reduced pressure gives a white solid which, after recrystallization from a mixture of ethyl ether and acetonitrile, gives 2.1 g of (3aRS,4RS,6SR,7aSR)-6-hydroxymethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]perhydroisoindol-4-ol in the form of white crystals. M.p.=162° C.

Workup

  1. washwashed with 30 cm3 of water
  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 0.06-0.20 mm, height [lacuna]cm) in ethyl acetate
  5. additionin a mixture of ethyl acetate and methanol (95:5 by volume)
  6. customDrying under reduced pressure
  7. customgives a white solid which
  8. customafter recrystallization
  9. additionfrom a mixture of ethyl ether and acetonitrile

Sources & evidence

ORD record
ord-65b00074b40645349a3ec6ec5f9eee4a
Source dataset
uspto-grants-1998_04
Patent number
US05739351

Reaction notes

Loading…