Boron trifluoride etherate → HCID 54368796, compound

HRID 1788674Notes

Reaction equation

HRID 1788674 reaction equation
B(F)(F)F.CCOCC.C(O[CH:13]([O:17][CH2:18][CH3:19])[O:14][CH2:15][CH3:16])C.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][C@H:27]1[CH2:32][CH2:31][C@H:30]2[C@H:33]3[C@H:43]([CH2:44][CH2:45][C@:28]12[CH3:29])[C@:41]1([CH3:42])[C@H:36]([CH2:37][C:38](=[O:46])[CH2:39][CH2:40]1)[CH2:35][CH2:34]3.C(N(C(C)C)CC)(C)C>ClCCl>[CH2:18]([O:17][CH:13]([O:14][CH2:15][CH3:16])[C@@H:39]1[CH2:40][C@@:41]2([CH3:42])[C@@H:36]([CH2:35][CH2:34][C@@H:33]3[C@@H:43]2[CH2:44][CH2:45][C@@:28]2([CH3:29])[C@H:30]3[CH2:31][CH2:32][C@@H:27]2[O:26][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][O:20]2)[CH2:37][C:38]1=[O:46])[CH3:19]

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 31214Ethyl orthoformateHCID 81531DiisopropylethylamineHCID 12889207HCID 12889207, compound

Product 1

HCID 54368796HCID 54368796, compoundYield 49.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Under an argon atmosphere at less than -30° C. boron trifluoride etherate (100 ml., 115.4 g., 0.704 mole) was added to a solution of triethylorthoformate (109.5 ml., 97.56 g., 0.658 mole) in dichloromethane (300 ml.). The temperature was raised to 0° C., kept there for 15 min., then lowered to -70° C. A solution of (5α,17β)-17-[(tetrahydro-2H-pyran-2-yl)oxy]androstan-3-one (0.3 mole) in dichloromethane (250 ml.+50 ml. for rinsing) was then added, followed by diisopropylethylamine (166.5 ml., 123.5 g., 0.955 mole), the latter while maintaining the temperature at less then -55° C. The temperature was lowered to -70° C. for 1 hr. The mixture was then quenched in aqueous sodium bicarbonate solution (3 1., made by dissolving 300 g. of sodium bicarbonate in 3.5 1. of water). The layers were separated. The aqueous layer was extracted with dichloromethane (250 ml.). The combined dichloromethane layers were washed twice with cold hydrochloric acid (2N, 1200 ml., 600 ml.), then with half-saturated aqueous sodium bicarbonate solution (800 ml.), dried and stripped of dichloromethane. The residue was triturated with hexane, affording (2α,5α,17β)-2-(diethoxymethyl)-17-[(tetrahydro-2H-pyran-2-yl)oxy]androstan-3-one (70.57 g., 49% yield, m.r. 165°-168° C.).

Workup

  1. customlowered to -70° C
  2. temperaturethe latter while maintaining the temperature at less then -55° C
  3. waitThe temperature was lowered to -70° C. for 1 hr
  4. customThe mixture was then quenched in aqueous sodium bicarbonate solution (3 1., made by dissolving 300 g. of sodium bicarbonate in 3.5 1. of water)
  5. customThe layers were separated
  6. extractionThe aqueous layer was extracted with dichloromethane (250 ml.)
  7. washThe combined dichloromethane layers were washed twice with cold hydrochloric acid (2N, 1200 ml., 600 ml.)
  8. dry with materialwith half-saturated aqueous sodium bicarbonate solution (800 ml.), dried
  9. customThe residue was triturated with hexane

Sources & evidence

ORD record
ord-5fb9655e153e473989509987f2918670
Source dataset
uspto-grants-1987_08
Patent number
US04684636

Reaction notes

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