Hydrochloric Acid → 3-Hydroxy-17-methyleneestra-1,3,5(10)-triene-2-carboxaldehyde

HRID 343307

Reaction equation

HRID 343307 reaction equation
[Mg].BrCC.[CH2:5]=[C:6]1[CH2:11][CH2:10][C@H:9]2[C@H:12]3[C@H:21]([CH2:22][CH2:23][C@:7]12[CH3:8])[C:20]1[CH:19]=[CH:18][C:17]([OH:24])=[CH:16][C:15]=1[CH2:14][CH2:13]3.CN(C)P(=O)(N(C)C)N(C)C.[CH2:36]=[O:37].Cl>C1COCC1.C1C=CC=CC=1>[OH:24][C:17]1[C:18]([CH:36]=[O:37])=[CH:19][C:20]2[C@@H:21]3[C@H:12]([C@H:9]4[C@@:7]([CH2:23][CH2:22]3)([CH3:8])[C:6](=[CH2:5])[CH2:11][CH2:10]4)[CH2:13][CH2:14][C:15]=2[CH:16]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 6332Ethyl BromideHCID 12679HexamethylphosphoramideHCID 5462224MagnesiumHCID 1445855217-Methylene-estra-1,3,5(10)-trien-3-ol

Product 1

HCID 542724493-Hydroxy-17-methyleneestra-1,3,5(10)-triene-2-carboxaldehydeYield 78.2%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of magnesium (0.365 g, 15 mmol) in THF (3.0 mL) was added bromoethane (1.5 mL, 20 mmol) dissolved in THF (3.0 mL) at room temperature. 17-Methyleneestra-1,3,5(10)-trien-3-ol (19, 0.805 g, 3.0 mmol) dissolved in THF (7.5 mL) was added to the reaction mixture, and stirring continued for 30 min. The solvent was removed at reduced pressure, and to the residue were added benzene (35 mL), hexamethylphosphoric triamide (1.4 mL, 7.5 mmol) and paraformaldehyde (0.630 g). Stirring was continued for 6 h at 80° C. After the reaction mixture was cooled to room temperature, 5N HCl (15 mL) was added and the mixture extracted with EtOAc. The combined organic layers were washed with H2O, then with saturated aqueous NaCl, and dried (Na2SO4). The desiccant was filtered and the solvent was evaporated at reduced pressure. The residue was purified by column chromatography (silica gel) using n-hexane:AcOEt (10:1→3:1, v/v) to afford 0.695 g of 23 (78% yield), m.p. 128°-130° C.

Workup

  1. additionwas added to the reaction mixture
  2. customThe solvent was removed at reduced pressure
  3. stirringStirring
  4. waitwas continued for 6 h at 80° C
  5. extractionthe mixture extracted with EtOAc
  6. washThe combined organic layers were washed with H2O
  7. dry with materialwith saturated aqueous NaCl, and dried (Na2SO4)
  8. filtrationThe desiccant was filtered
  9. customthe solvent was evaporated at reduced pressure
  10. customThe residue was purified by column chromatography (silica gel)

Sources & evidence

ORD record
ord-e7eaae67874d4c4495113894041f5713
Source dataset
uspto-grants-1999_01
Patent number
US05861388

Linked notes

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