3,4-dihydro-2H-pyran → HCID 70583546, compound

HRID 1701437Notes

Reaction equation

HRID 1701437 reaction equation
Br[C@H:2]1[CH2:21][C@@:20]2([CH3:22])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:19]2[C@@H:18]([O:23][C:24](=[O:31])[CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[CH2:17][C@@:16]2([CH3:32])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:13](=[O:15])[CH3:14])[CH2:4][C@@H:3]1[OH:33].O1C=CCCC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1.CO>[CH2:27]([N:26]([CH2:25][C:24]([O:23][C@H:18]1[CH2:17][C@@:16]2([CH3:32])[C@@H:9]([CH2:10][CH2:11][C@@H:12]2[C:13](=[O:15])[CH3:14])[C@H:8]2[C@H:19]1[C@:20]1([CH3:22])[C@@H:5]([CH2:6][CH2:7]2)[CH2:4][C@H:3]([OH:33])[CH:2]=[CH:21]1)=[O:31])[CH2:29][CH3:30])[CH3:28]

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 22810343HCID 22810343, compound

Product 1

HCID 70583546HCID 70583546, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 887MethanolSolvent

Procedure

2β-Bromo-11β-diethylaminoacetoxy-3α-hydroxy-5α-pregnan-20-one (1 g) was stirred and warmed with dihydropyran (2 ml) in benzene (40 ml) containing p-toluene sulphonic acid monohydrate (406 mg) until a clear solution was achieved. After 20 mins, the mixture was washed with excess sodium bicarbonate solution and brine (2x) and dried with magnesium sulphate. Evaporation of the benzene left a gum which was dissolved in N,N-dimethylformamide (25 ml) and stirred at 120° with calcium carbonate (2.5 g) and lithium bromide (3.3 g) for 5.5 hours. When reaction was complete, the mixture was diluted with methanol and filtered. The methanolic filtrate was made acidic by addition of 2N hydrochloric acid (4 ml). After 4 hours at 20°, excess sodium bicarbonate solution was added and the mixture evaporated to a small volume, extracted with ethyl acetate (twice) and the combined organic solutions were washed with brine (twice) and dried with magnesium sulphate. Evaporation of the solvent left a gum which was filtered through silica gel (30 g) in ethyl acetate and the eluate concentrated. Further purification was achieved by preparative TLC and recrystallisation from aqueous methanol to give title compound m.p. 134°-138°, [α]D +51.6° (270 mg).

Workup

  1. washthe mixture was washed with excess sodium bicarbonate solution and brine (2x)
  2. dry with materialdried with magnesium sulphate
  3. customEvaporation of the benzene
  4. waitleft a gum which
  5. dissolutionwas dissolved in N,N-dimethylformamide (25 ml)
  6. customWhen reaction
  7. filtrationfiltered
  8. additionThe methanolic filtrate was made acidic by addition of 2N hydrochloric acid (4 ml)
  9. waitAfter 4 hours at 20°
  10. additionexcess sodium bicarbonate solution was added
  11. customthe mixture evaporated to a small volume
  12. extractionextracted with ethyl acetate (twice) and the combined organic solutions
  13. washwere washed with brine (twice) and
  14. dry with materialdried with magnesium sulphate
  15. customEvaporation of the solvent
  16. waitleft a gum which
  17. filtrationwas filtered through silica gel (30 g) in ethyl acetate
  18. customFurther purification
  19. customwas achieved by preparative TLC and recrystallisation from aqueous methanol

Sources & evidence

ORD record
ord-1269d63db7ba4a8a97f6be0351f1e314
Source dataset
uspto-grants-1980_03
Patent number
US04192871

Reaction notes

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