2-Methoxyphenylacetic acid → HCID 15289540, compound

HRID 2211416Notes

Reaction equation

HRID 2211416 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>C(Cl)Cl>[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][N:35]([C:22](=[O:24])[CH2:21][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH3:13])[CH2:36]3)[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 15289540HCID 15289540, 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 methylene chloride. The mixture is stirred at room temperature for I hour and a suspension of 0.7 g of (3aS,4S,7aS)-4,7,7-triphenyl-perhydroisoindol-4-ol hydrochloride in 20 cm3 of dry methylene chloride 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 methylene chloride, 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 over 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 crystallised 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)-acetyl]-perhydroisoindol-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 over 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 crystallised in 16 cm3 of acetonitrile
  10. filtrationThe crystals are filtered off
  11. customdried

Sources & evidence

ORD record
ord-e6ca78faf1154b9b82c33ec9afec4248
Source dataset
uspto-grants-1995_10
Patent number
US05463077

Reaction notes

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