4-Toluenesulfonyl chloride → HCID 86752416, compound

HRID 1599146Notes

Reaction equation

HRID 1599146 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.C(N(CC)CC)C.[OH:19][CH2:20][C@@H:21]1[CH2:29][C@@H:28]2[C@@H:24]([CH2:25][N:26]([C:30](=[O:41])[C@H:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[O:39][CH3:40])[CH3:32])[CH2:27]2)[C@@:23]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[F:49])([OH:42])[CH2:22]1>ClCCl>[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O:19][CH2:20][C@@H:21]2[CH2:29][C@@H:28]3[C@@H:24]([CH2:25][N:26]([C:30](=[O:41])[C@H:31]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[O:39][CH3:40])[CH3:32])[CH2:27]3)[C@@:23]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[F:49])([OH:42])[CH2:22]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 67660570HCID 67660570, compound

Product 1

HCID 86752416HCID 86752416, compoundYield 59.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4.2 g of p-toluenesulphonyl chloride and then 3.1 cm3 of triethylamine are added at room temperature to a solution of 1.17 g of (3aS,4S,6R,7aR)-6-hydroxymethyl-4-(2-fluorophenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydroisoindol-4-ol in 30 cm3 of dichloromethane. The reaction mixture is stirred at this temperature for 18 hours, then washed with twice 25 cm3 of water and then with 25 cm3 of saturated aqueous sodium chloride solution, 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 0.04-0.06 mm, diameter 2.8 cm, height 25 cm), eluting under a pressure of 0.8 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (60:40 by volume) and collecting fractions of 25 cm3. Fractions 22 to 35 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.95 g of (3aS,4S,6R,7aR)-6-p-toluenesulphonyloxymethyl-4-(2-fluorophenyl)-2-[(S)-2-(2-methoxyphenyl) propionyl]perhydroisoindol-4-ol is obtained in the form of a thick white foam.

Workup

  1. washwashed with twice 25 cm3 of water
  2. dry with materialwith 25 cm3 of saturated aqueous sodium chloride solution, dried 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 0.04-0.06 mm, diameter 2.8 cm, height 25 cm)
  5. washeluting under a pressure of 0.8 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (60:40 by volume)
  6. customcollecting fractions of 25 cm3
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-425bb139bc2f4fd2965533bec7c768d2
Source dataset
uspto-grants-1998_04
Patent number
US05739351

Reaction notes

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