Morpholinosulfur trifluoride → (3aR, 7R,7aR)-2-t-butoxycarbonyl-4,4-diphenyl-7-fluoroperhydroisoindole

HRID 2400005Notes

Reaction equation

HRID 2400005 reaction equation
O1CCN(S(F)(F)[F:8])CC1.[C:11]1([C:17]2([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C@H:25]3[C@H:21]([CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24]3)[C@@H:20](O)[CH2:19][CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>ClCCl>[C:11]1([C:17]2([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:18][CH2:19][C@@H:20]([F:8])[C@@H:21]3[C@H:25]2[CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22]3)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 2733258Morpholinosulfur trifluorideHCID 11003741(3aR,4S,7aR)-2-t-butoxycarbonyl-7,7-diphenyl-4-perhydroisoindolol

Product 1

HCID 54399787(3aR, 7R,7aR)-2-t-butoxycarbonyl-4,4-diphenyl-7-fluoroperhydroisoindole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 3.5 cm3 of morpholinosulphur trifluoride in 50 cm3 of dichloromethane is added to a solution, cooled to +5° C., of 9.4 g of (3aR,4S,7aR)-7,7-diphenyl-2-tert-butyloxycarbonyl-4-perhydroisoindolol in 250 cm3 of dry dichloromethane. The reaction mixture is stirred for 4 hours at +5° C. and then diluted with 300 cm3 of dichloromethane, washed with 250 cm3 of an aqueous solution of sodium hydrogen carbonate, dried over magnesium sulphate, filtered 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 3.5 cm, height 42 cm), eluting under a nitrogen pressure of 0.5 bar with a cyclohexane and ethyl acetate mixture (90/10 by volume) and collecting fractions of 120 cm3. Fractions 13 to 17 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from cyclohexane. 2.55 g of (3aR,7R,7aR)-4,4-diphenyl-7-fluoro-2-tert-butyloxycarbonylperhydroisoindole are obtained in the form of white crystals; melting point 202° C.

Workup

  1. washwashed with 250 cm3 of an aqueous solution of sodium hydrogen carbonate
  2. dry with materialdried over magnesium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3.5 cm, height 42 cm)
  6. washeluting under a nitrogen pressure of 0.5 bar with a cyclohexane and ethyl acetate mixture (90/10 by volume)
  7. customcollecting fractions of 120 cm3
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is crystallized from cyclohexane

Sources & evidence

ORD record
ord-7c28c2ad026143158cdc622436ba1432
Source dataset
uspto-grants-1995_09
Patent number
US05451601

Reaction notes

Loading…