Hydrochloric Acid → (3aR,4S,7aR)-2-t-butoxycarbonyl-7,7-diphenyl-4-perhydroisoindolol

HRID 1721194Notes

Reaction equation

HRID 1721194 reaction equation
[BH4-].[Na+].[C:3]1([C:9]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C@H:17]3[C@H:13]([CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16]3)[C:12](=[O:25])[CH2:11][CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl>CO>[C:3]1([C:9]2([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C@H:17]3[C@H:13]([CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16]3)[C@@H:12]([OH:25])[CH2:11][CH2:10]2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 15379415(3aR, 7aR)-7,7-diphenyl-2-tert-butyloxycarbonyl-4-perhydroisoindolone

Product 1

HCID 11003741(3aR,4S,7aR)-2-t-butoxycarbonyl-7,7-diphenyl-4-perhydroisoindololYield 46.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 1 g of sodium borohydride in 200 cm3 of methanol is added dropwise over 40 minutes to a solution, cooled to +4° C., of 17.8 g of (3aR, 7aR)-7,7-diphenyl-2-tert-butyloxycarbonyl-4-perhydroisoindolone in one litre of methanol, followed by 10 drops of lye. The reaction mixture is stirred for 3 hours at +4° C. and then 2 cm3 of a 0.1N aqueous solution of hydrochloric acid are added and the mixture is concentrated to dryness under reduced pressure (2.7 kPa). The residue is dissolved in 350 cm3 of dichloromethane, washed with 100 cm3 of water and then with 50 cm3 of a saturated solution of sodium chloride, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from 40 cm3 of ethyl ether. The crystals obtained are drained and dried. 8.4 g of (3aR, 4S, 7aR)-7,7-diphenyl-2-tert-butyloxycarbonyl-4-perhydroisoindolol are obtained in the form of white crystals; melting point 190° C. The crystallization mother liquors are 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 4 cm, height 33 cm), eluting under a nitrogen pressure of 0.4 bar with a dichloromethane and methanol mixture (96/4 by volume) and collecting fractions of 20 cm3. Fractions 18 to 21 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). 1.88 g of (3aR, 4R,7aR)-7,7-diphenyl-2-tert-butyloxycarbonyl-4-perhydroisoindolol are obtained in the form of a white meringue. Fractions 26 to 31 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from 5 cm3 of ethyl ether. 2.88 g of (3aR, 4S, 7aR)-7,7-diphenyl-2-tert-butyloxycarbonyl-4-perhydroisoindolol are additionally obtained in the form of white crystals; melting point 190° C.

Workup

  1. concentrationthe mixture is concentrated to dryness under reduced pressure (2.7 kPa)
  2. dissolutionThe residue is dissolved in 350 cm3 of dichloromethane
  3. washwashed with 100 cm3 of water
  4. dry with materialwith 50 cm3 of a saturated solution of sodium chloride, dried over magnesium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is crystallized from 40 cm3 of ethyl ether
  7. customThe crystals obtained
  8. customdried

Sources & evidence

ORD record
ord-2db7b7d82d25472ab874778ec6aebdd6
Source dataset
uspto-grants-1996_04
Patent number
US05508433

Reaction notes

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