Benzhydrylamine → N-Diphenylmethyl-3-methoxyestra-1,3,5(10)-trien-17beta-amine

HRID 1741940Notes

Reaction equation

HRID 1741940 reaction equation
[NH2:1][CH:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:15][C@@:16]12[C:24](=O)[CH2:23][CH2:22][C@H:21]1[C@@H:20]1[CH2:26][CH2:27][C:28]3[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=3[C@H:19]1[CH2:18][CH2:17]2.C([BH3-])#N.[Na+]>CO.C(O)(=O)C.C1COCC1>[C:9]1([CH:2]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[NH:1][C@H:24]2[CH2:23][CH2:22][C@H:21]3[C@H:20]4[C@H:19]([CH2:18][CH2:17][C@:16]23[CH3:15])[C:29]2[CH:30]=[CH:31][C:32]([O:34][CH3:35])=[CH:33][C:28]=2[CH2:27][CH2:26]4)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 3

HCID 7036BenzhydrylamineHCID 92895(+)-Estrone 3-methyl etherHCID 5003444Sodium cyanoborohydride

Product 1

HCID 67726218N-Diphenylmethyl-3-methoxyestra-1,3,5(10)-trien-17beta-amine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of aminodiphenylmethane (5.50 g) in methanol (100 ml) was stirred at room temperature. Added sequentially to this solution were glacial acetic acid (1.8 ml, 1.8 g), estrone methyl ether (8.52 g), sodium cyanoborohydride (2.3 g), and THF (80 ml). The mixture was stirred at room temperature for 8 days. Additional NaB(CN)H3 (1.5 g), amine (5.5 g), and acetic acid (1.8 g) were added after four days of the reaction time. Excess solvent was removed under reduced pressure and water (300 ml) was added to the solid residue. The mixture was made alkaline with 50% aqueous NaOH and was extracted with ether (3×). The extracts were dried (MgSO4), filtered, and concentrated, giving an oily residue. This crude product was chromatographed (500 g silica gel, 5% ethyl acetate-hexane, 350 ml fractions) on a gravity column. The desired product was eluted in fractions 4-7, and after recrystalli-zation from methanol gave a first crop of crystals, mp 127° -129° C, and a second crop. A sample was recrystallized again from methanol and gave an analytical sample of the title compound, mp 127°-129° C. (PLA2, diabetes)

Workup

  1. additionAdded sequentially to this solution
  2. customExcess solvent was removed under reduced pressure and water (300 ml)
  3. additionwas added to the solid residue
  4. extractionwas extracted with ether (3×)
  5. dry with materialThe extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customgiving an oily residue
  9. customThis crude product was chromatographed (500 g silica gel, 5% ethyl acetate-hexane, 350 ml fractions) on a gravity column
  10. washThe desired product was eluted in fractions 4-7
  11. customafter recrystalli-zation from methanol gave a first crop of crystals, mp 127° -129° C
  12. customA sample was recrystallized again from methanol

Sources & evidence

ORD record
ord-9304a21fd4224ffeac88677fca4d4efc
Source dataset
uspto-grants-1994_08
Patent number
US05334712

Reaction notes

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