2-Methoxyphenylacetic acid → HCID 86752413, compound

HRID 1599137Notes

Reaction equation

HRID 1599137 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][C:17]([OH:19])=O.CN(C)CCCN=C=NCC.Cl.[C:32]([CH2:34][C@@H:35]1[CH2:43][C@@H:42]2[C@@H:38]([CH2:39][NH:40][CH2:41]2)[C@@:37]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[O:51][CH3:52])([OH:44])[CH2:36]1)#[N:33]>ClCCl.O.OC1C2N=NNC=2C=CC=1>[C:32]([CH2:34][C@@H:35]1[CH2:43][C@@H:42]2[C@@H:38]([CH2:39][N:40]([C:17](=[O:19])[CH2:16][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[O:9][CH3:8])[CH2:41]2)[C@@:37]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[O:51][CH3:52])([OH:44])[CH2:36]1)#[N:33]

Participants

7

Reactant 4

HCID 71342-Methoxyphenylacetic acidHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 67660461HCID 67660461, compound

Product 1

HCID 86752413HCID 86752413, compoundYield 32.5%

Reagents, catalysts & solvents 2

HCID 178526939HCID 178526939, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

1.82 cm3 of triethylamine, 2.0 g of 2-methoxy-phenylacetic acid, 25 mg of hydroxybenzotriazole hydrate and 2.54 g of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide are added to a solution of 3.96 g of (3aS,4S,6S,7aR)-6-cyanomethyl-4-(2-methoxyphenyl)-perhydroisoindol-4-ol hydrochloride in 60 cm3 of dichloromethane. The reaction mixture is stirred at room temperature for 20 hours, washed with 50 cm3 of water, dried over magnesium sulphate and concentrated to dryness under reduced pressure. The residue is chromatographed on a silica gel column (particle size 0.06-0.20 mm, diameter 3.6 cm, height 30 cm) under a pressure of 0.5 bar of nitrogen with ethyl acetate, collecting fractions of 100 cm3. Fractions 6 to 16 are concentrated to dryness under reduced pressure (2.7 kPa), the residue is recrystallized from ethyl acetate and then from ethanol, and the crystals are filtered, washed with a little ethanol and ethyl ether, drained and then dried under reduced pressure (2.7 kPa). 1.7 g of (3aS, 4S, 6S, 7aR)-6-cyanomethyl-4-(2-methoxyphenyl)-2-[(2-methoxyphenyl) acetyl]-perhydroisoindol-4-ol are obtained in the form of white crystals. M.p.K =160° C.

Workup

  1. washwashed with 50 cm3 of water
  2. dry with materialdried over magnesium sulphate
  3. concentrationconcentrated to dryness under reduced pressure
  4. customThe residue is chromatographed on a silica gel column (particle size 0.06-0.20 mm, diameter 3.6 cm, height 30 cm) under a pressure of 0.5 bar of nitrogen with ethyl acetate
  5. customcollecting fractions of 100 cm3
  6. concentrationFractions 6 to 16 are concentrated to dryness under reduced pressure (2.7 kPa)
  7. customthe residue is recrystallized from ethyl acetate
  8. filtrationfrom ethanol, and the crystals are filtered
  9. washwashed with a little ethanol and ethyl ether
  10. customdried under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-da686f4638994f92bf848e89a3774600
Source dataset
uspto-grants-1998_04
Patent number
US05739351

Reaction notes

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