(1R,2S)-Tranylcypromine → Methyl 4-{[3-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)-1-pyrrolidinyl]methyl}benzoate

HRID 529315

Reaktionsgleichung

Reaktionsgleichung von HRID 529315
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:11]([CH:13]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=2)[CH2:14]1)=O.C([BH3-])#N.[Na+]>CO>[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH:10][CH2:11][CH:13]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=3)[CH2:14]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Komponenten

5

Edukt 3

HCID 19493(1R,2S)-TranylcypromineHCID 5003444Sodium cyanoborohydrideHCID 86708239Methyl 4-((3-formylpyrrolidin-1-yl)methyl)benzoate

Produkt 1

HCID 68385362Methyl 4-{[3-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)-1-pyrrolidinyl]methyl}benzoateAusbeute 40,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A solution of (1R,2S)-2-phenylcyclopropanamine (300 mg, 2.252 mmol) and methyl 4-((3-formylpyrrolidin-1-yl)methyl)benzoate (501 mg, 2.027 mmol) in methanol (50 mL) was heated to reflux for 5 minutes. The reaction mixture was cooled to room temperature and sodium cyanoborohydride (212 mg, 3.38 mmol) was added. The reaction was stirred at room temperature for 16 hours. After concentrating, dichloromethane was added and the solution was washed with water, dried over MgSO4, filtered and concentrated. HPLC purification (reverse phase) was performed with a Gemini NX 5u C18 110A, AXIA. 100×30.00 mm 5 micron column. A 7 minute gradient run (0% AcCN/H2O, 0.1% Formic Acid to 55% ACN/H2O, 0.1% Formic Acid) with UV detection at 214 nm was utilized. Added 1 ml of 1N HCl to fractions containing product and concentrated. Only the desired ester was seen by LC/MS of fractions before concentrating. Obtained 300 mg of a mixture of diastereomers.

Aufarbeitung

  1. temperatureto reflux for 5 minutes
  2. concentrationAfter concentrating
  3. additiondichloromethane was added
  4. washthe solution was washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customHPLC purification (reverse phase)
  9. customA 7 minute gradient run (0% AcCN/H2O, 0.1% Formic Acid to 55% ACN/H2O, 0.1% Formic Acid)
  10. additionAdded 1 ml of 1N HCl to fractions
  11. additioncontaining product
  12. concentrationconcentrated
  13. concentrationbefore concentrating

Quellen und Nachweise

ORD-Eintrag
ord-3856b23c77d449aebf03d8305e376665
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346840B2

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