Triethylamine → (3aR,7aR)-2-[(S)-alpha-fluorophenylacetyl]-7,7-diphenyl-4-perhydroisoindolone

HRID 1029917Notes

Reaction equation

HRID 1029917 reaction equation
Cl.[C:2]1([C:8]2([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@H:16]3[C@H:12]([CH2:13][NH:14][CH2:15]3)[C:11](=[O:17])[CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:31][C@@H:32]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:33](Cl)=[O:34].FF>ClCCl.N1C=CC=CC=1>[F:31][C@@H:32]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:33]([N:14]1[CH2:13][C@H:12]2[C@H:16]([C:8]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:9][CH2:10][C:11]2=[O:17])[CH2:15]1)=[O:34]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24524FluorineHCID 22843247(3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochlorideHCID 57201156(S)-alpha-fluorophenylacetyl chloride

Product 1

HCID 22843235(3aR,7aR)-2-[(S)-alpha-fluorophenylacetyl]-7,7-diphenyl-4-perhydroisoindolone

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of (3aR,7aR)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.12 g), triethylamine (0.9 cc) and pyridine (0.5 cc) in dichloromethane (30 cc) is added, at 0° C., to a solution of (S)-α-fluorophenylacetyl chloride [prepared from acid (1 g) by the method described by S. Hamman et al., J. Fluorine Chem., 37, 85 (1987)] in dichloromethane (20 cc). The reaction mixture is stirred for 2 hours allowing the temperature to return to 20° C. and is then concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in ethyl acetate (100 cc). The solution is washed with water (2×100 cc) and then with saturated sodium bicarbonate solution (50 cc) and with saturated sodium chloride solution (50 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 3 cm, height 40 cm), eluting under a nitrogen pressure of 0.7 bar with ethyl acetate and collecting 100 cc fractions to give (3aR,7aR)-2-[(S)-α-fluorophenylacetyl]-7,7-diphenyl-4-perhydroisoindolone (1 g) in the form of a white meringue.

Workup

  1. customto return to 20° C.
  2. concentrationis then concentrated to dryness under reduced pressure (2.7 kPa)
  3. washThe solution is washed with water (2×100 cc)
  4. dry with materialwith saturated sodium bicarbonate solution (50 cc) and with saturated sodium chloride solution (50 cc), dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  7. customThe residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 3 cm, height 40 cm)
  8. washeluting under a nitrogen pressure of 0.7 bar with ethyl acetate
  9. customcollecting 100 cc fractions

Sources & evidence

ORD record
ord-397a068271f745c793e06320082a081b
Source dataset
uspto-grants-1992_04
Patent number
US05102667

Reaction notes

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