2-Methoxyphenylacetic acid → HCID 67736937, compound

HRID 375430Notes

Reaction equation

HRID 375430 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][C:22]([OH:24])=O.Cl.[C:26]1([C@:32]2([OH:53])[CH2:40][CH2:39][C:38]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C@@H:37]3[C@H:33]2[CH2:34][NH:35][CH2:36]3)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(CC)CC)C>ClCCl>[C:26]1([C@:32]2([OH:53])[CH2:40][CH2:39][C:38]([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)([C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)[C@@H:37]3[C@H:33]2[CH2:34][NH:35][CH:36]3[C:22](=[O:24])[CH2:21][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH3:13])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 71342-Methoxyphenylacetic acidHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 67736920HCID 67736920, compound

Product 1

HCID 67736937HCID 67736937, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

0.28 g of carbonyldiimidazole is added to a solution of 0.28 g of (2-methoxyphenyl)acetic acid in 20 cm3 of dry dichloromethane. The mixture is stirred at room temperature for 1 hour and a suspension of 0.7 g of (3aS,4S,7aS)-4,7,7-triphenylperhydroisoindol-4-ol hydrochloride in 20 cm3 of dry dichloromethane and then 0.48 cm3 of triethylamine are subsequently added in succession. The reaction mixture is stirred at room temperature for 24 hours, diluted with 100 cm3 of dichloromethane, washed with 100 cm3 of water (twice) and then with 100 cm3 of an aqueous saturated solution of sodium chloride, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 2 cm, height 16 cm) by eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (55/45 by volume) and collecting fractions of 20 cm3. Fractions 7 to 8 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized in 16 cm3 of acetonitrile. The crystals are filtered off and dried. 0.3 g of (3aS,4S,7aS)-4,7,7-triphenyl-2-(2-methoxyphenyl)acetylperhydroisoindol-4-ol is obtained in the form of white crystals which melt at 236° C.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 24 hours
  2. washwashed with 100 cm3 of water (twice) and then with 100 cm3 of an aqueous saturated solution of sodium chloride
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue is chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 2 cm, height 16 cm)
  6. washby eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (55/45 by volume)
  7. customcollecting fractions of 20 cm3
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is crystallized in 16 cm3 of acetonitrile
  10. filtrationThe crystals are filtered off
  11. customdried

Sources & evidence

ORD record
ord-94f3805f963548eb9eb033d14c0c13c4
Source dataset
uspto-grants-1996_01
Patent number
US05484804

Reaction notes

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