Estrone → (+)-Estrone 3-methyl ether

HRID 1637575Notes

Reaction equation

HRID 1637575 reaction equation
[CH3:1][C@@:2]12[C:18](=[O:19])[CH2:17][CH2:16][C@H:15]1[C@H:14]1[C@@H:5]([C:6]3[CH:7]=[CH:8][C:9]([OH:20])=[CH:10][C:11]=3[CH2:12][CH2:13]1)[CH2:4][CH2:3]2.[C:21]([O-])([O-])=O.[K+].[K+].CI>CO>[CH3:21][O:20][C:9]1[CH:8]=[CH:7][C:6]2[C@@H:5]3[C@H:14]([C@H:15]4[C@@:2]([CH2:3][CH2:4]3)([CH3:1])[C:18](=[O:19])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]=2[CH:10]=1

Participants

5

Reactant 3

HCID 5870EstroneHCID 6328Methyl iodideHCID 11430Potassium Carbonate

Product 1

HCID 92895(+)-Estrone 3-methyl etherYield 99.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Estrone (1, 100.0 g, 370 mmol) was dissolved in MeOH (1.5 L), followed by the addition of K2CO3 (300.0 g, 2.17 mol). MeI (310 mL, 4.98 mol) was added and the mixture stirred at room temperature for 70 h. The reaction mixture was concentrated in vacuo to remove some of the MeOH and was then poured into ice water forming a precipitate. The solid was collected and dried by partitioning into CH2Cl2. The organic layer was dried over MgSO4, and the solvent was removed in vacuo to yield compound 2 (105.0 g) as white crystals in quantitative yield. 1H NMR (250 MHz, CDCl3); δ 0.91 (s, 3, C-18 H), 3.78 (s, 3, MeO), 6.65 (s, 1, C-4 H), 6.72 (d, 1, J=8.57 Hz, C-2 H), 7.21 (d, 1, J=8.57 Hz, C-1 H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto remove some of the MeOH
  3. additionwas then poured into ice water forming a precipitate
  4. customThe solid was collected
  5. customdried
  6. customby partitioning into CH2Cl2
  7. dry with materialThe organic layer was dried over MgSO4
  8. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-3fcdb4666ce244c09d00c1fdc84c6c5d
Source dataset
uspto-grants-2000_03
Patent number
US06043235

Reaction notes

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