Boron trifluoride etherate → HCID 22983882, compound

HRID 1263482Notes

Reaction equation

HRID 1263482 reaction equation
F[B-](F)(F)F.B(F)(F)[F:7].CCOCC.N[C:16]1[CH:17]=[CH:18][C:19]2[CH2:20][CH2:21][C@@H:22]3[C@@H:31]([C:32]=2[CH:33]=1)[CH2:30][CH2:29][C@@:27]1([CH3:28])[C@H:23]3[CH2:24][CH2:25][CH2:26]1.C(ON=O)(C)(C)C>C(Cl)Cl.CCCCC>[F:7][C:17]1[CH:16]=[CH:33][C:32]2[C@@H:31]3[C@H:22]([C@H:23]4[C@@:27]([CH2:29][CH2:30]3)([CH3:28])[CH2:26][CH2:25][CH2:24]4)[CH2:21][CH2:20][C:19]=2[CH:18]=1

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 10906Tert-Butyl nitriteHCID 26255TetrafluoroborateHCID 22820969HCID 22820969, compound

Product 1

HCID 22983882HCID 22983882, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8003PentaneSolvent

Conditions

Temperature
-15 °C

Procedure

3-Fluoroestrone was synthesized from 2-aminoestrone by adapting the procedure reported by Doyle and Bryker (J. Org. Chem. 44, 1572-1574, 1979) for the synthesis of arenediaxonium tetrafluoroborate salts from aromatic amines. The procedure is as followed: To neat stirred boron trifluoride etherate (642 μL, 719 mg, 5.07 mmol) at −15° C. under Ar (g) was added a solution of 3-aminoestrone (101) (910 mg, 3.38 mmol) in dry CH2Cl2 (10 mL). After 15 min, a solution of t-butylnitrite (482 μL, 418 mg, 4.05 mmol) in dry CH2Cl2 (5 mL) was dropwise added. The now dark brown solution was stirred at −15° C. for 15 min, then at 0° C. for 30 min. Pentane was added to the solution and a gummy solid precipitated. The solvent was decanted and the residue was dried under vacuum to give a crude light brown solid. The neat solid was heated under vacuum at 70-80° C. in an oil bath for 15 min to give a crude orange solid. Purification by flash chromatography on SiO2 using 1:9 EtOAc/Hexanes gave 3-fluoroestrone (102) as a white solid (437 mg, 47%). M.p. 178° C.; [α]25D +152.0° (c 1.03, CDCl3); IR (ν) 3044, 3039, 2928, 1740 (CO), 1611, 1585, 1495, 1474, 1458, 1428, 1405, 1377, 1340, 1272, 1245, 1230, 1212, 1148, 1094, 1084, 1053, 1008, 908, 889, 817, 784, 718, 704, 642, 620, 580, 564, 467 cm−1; 1H NMR (CDCl3) δ 0.92 (3H, s), 1.37-1.70 (6H, m), 1.93-2.44 (6H, m), 2.52 (1H, dd, J=18.8 Hz, J′=9.0 Hz), 2.91 (2H, dd, J=8.4 Hz, J′=3.8 Hz), 6.82 (2H, dq, J=8.3 Hz, J′=2.8 Hz), 7.23 (1H, dd, J=8.5 Hz, J′=5.8 Hz); 13C NMR (CDCl3) δ 13.8, 21.6, 25.9, 26.3, 29.5, 31.5, 35.9, 38.1, 44.0, 47.9, 50.4, 112.5 (d, J=21.6 Hz), 115.1 (d, J=19.7 Hz), 126.8 (d, J=7.5 Hz), 135.3, 138.7, 161.0 (d, J=244.3 Hz), 220.7.

Workup

  1. custom3-Fluoroestrone was synthesized from 2-aminoestrone
  2. waitat 0° C. for 30 min
  3. customa gummy solid precipitated
  4. customThe solvent was decanted
  5. customthe residue was dried under vacuum
  6. customto give a crude light brown solid
  7. temperatureThe neat solid was heated under vacuum at 70-80° C. in an oil bath for 15 min
  8. customto give a crude orange solid
  9. customPurification by flash chromatography on SiO2 using 1:9 EtOAc/Hexanes

Sources & evidence

ORD record
ord-5f20ee3b5717426d89d319b0e4e2648e
Source dataset
uspto-grants-2003_04
Patent number
US06541463B1

Reaction notes

Loading…