Diisopropylamine → 1alpha,3beta-Bis-(methoxymethoxy)-22-p-tolylsulfonyl-25-(2-tetrahydropyranyloxy)cholesta-5,7-dien-24-ol

HRID 1587628Notes

Reaction equation

HRID 1587628 reaction equation
[CH3:1][CH:2]([C@@H:14]1[C@:31]2([CH3:32])[C@H:17]([C:18]3[C@H:28]([CH2:29][CH2:30]2)[C@:26]2([CH3:27])[C:21]([CH2:22][C@@H:23]([O:37][CH2:38][O:39][CH3:40])[CH2:24][C@@H:25]2[O:33][CH2:34][O:35][CH3:36])=[CH:20][CH:19]=3)[CH2:16][CH2:15]1)[CH2:3][S:4]([C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1)(=[O:6])=[O:5].C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.[O:61]1[CH:63]([C:64]([CH3:73])([O:66][CH:67]2[CH2:72][CH2:71][CH2:70][CH2:69][O:68]2)[CH3:65])[CH2:62]1.[Cl-].[NH4+]>O1CCCC1.C(OCC)C.CCCCCC>[CH3:36][O:35][CH2:34][O:33][C@@H:25]1[C@@:26]2([CH3:27])[C:21](=[CH:20][CH:19]=[C:18]3[C@@H:28]2[CH2:29][CH2:30][C@@:31]2([CH3:32])[C@H:17]3[CH2:16][CH2:15][C@@H:14]2[C@H:2]([CH3:1])[CH:3]([S:4]([C:7]2[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=2)(=[O:6])=[O:5])[CH2:62][CH:63]([OH:61])[C:64]([O:66][CH:67]2[CH2:72][CH2:71][CH2:70][CH2:69][O:68]2)([CH3:73])[CH3:65])[CH2:22][C@@H:23]([O:37][CH2:38][O:39][CH3:40])[CH2:24]1

Participants

10

Reactant 6

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 197582721,2-Epoxy-3-methyl-3-(2-tetrahydropyranyloxy)butaneHCID 6778811320-Methyl-1alpha,3beta-bis(methoxymethoxy)-21-p-tolylsulfonylpregna-5,7-dieneHCID 178418339Butyllithium

Product 1

HCID 186523901alpha,3beta-Bis-(methoxymethoxy)-22-p-tolylsulfonyl-25-(2-tetrahydropyranyloxy)cholesta-5,7-dien-24-olYield 66.7%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-30 °C

Procedure

In 2 ml of tetrahydrofuran was dissolved 43 mg of 20-methyl-1α,3β-bis(methoxymethoxy)-21-p-tolylsulfonylpregna-5,7-diene and the solution was cooled in a dry ice-acetone bath under argon atmosphere. To the solution was added 0.35 ml of a lithium diisopropylamide solution prepared from 2 ml of a 1.5N hexane solution of butyllithium and 0.5 ml of diisopropylamine in 10 ml of tetrahydrofuran. The mixture was stirred at -30° C. for 30 minutes and then again cooled in a dry ice-acetone bath. A solution of 100 mg of 1,2-epoxy-3-methyl-3-(2-tetrahydropyranyloxy)butane in 1 ml of tetrahydrofuran was added and the resulting mixture was stirred at -20° C. for 7 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture and the mixture was allowed to warm to ambient temperature. Diethyl ether was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with diethyl ether. The organic layer was combined, washed in sequence with an aqueous solution of sodium hydrogen carbonate and an aqueous solution of sodium chloride, then dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give 38 mg of 1α,3β-bis-(methoxymethoxy)-22-p-tolylsulfonyl-25-(2 -tetrahydropyranyloxy)cholesta-5,7-dien-24-ol.

Workup

  1. temperaturethe solution was cooled in a dry ice-acetone bath under argon atmosphere
  2. temperatureagain cooled in a dry ice-acetone bath
  3. stirringthe resulting mixture was stirred at -20° C. for 7 hours
  4. temperatureto warm to ambient temperature
  5. customthe organic layer was separated
  6. extractionthe aqueous layer was extracted with diethyl ether
  7. washwashed in sequence with an aqueous solution of sodium hydrogen carbonate
  8. dry with materialan aqueous solution of sodium chloride, then dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f3f1b63c85394159aac0ed7aa30dc0e8
Source dataset
uspto-grants-1993_06
Patent number
US05218109

Reaction notes

Loading…