Sodium Hydroxide → 2,2-Dimethyl-3-(4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propanoic acid

HRID 534202

Reaktionsgleichung

Reaktionsgleichung von HRID 534202
FC(F)(F)C([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=O.[CH3:24][C:25]([CH3:32])([CH:30]=O)[C:26]([O:28]C)=[O:27].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.IC1C=CC=CC=1>[CH3:24][C:25]([CH3:32])([CH2:30][N:10]1[CH2:9][CH2:8][CH:7]([CH2:6][NH:5][C@@H:13]2[CH2:15][C@H:14]2[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:12][CH2:11]1)[C:26]([OH:28])=[O:27]

Komponenten

7

Edukt 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 11137194Methyl 2,2-dimethyl-3-oxopropanoate2×HCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

Produkt 1

HCID 683884982,2-Dimethyl-3-(4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propanoic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 11575IodobenzeneLösungsmittel2×

Versuchsvorschrift

To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (130 mg, 0.398 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 2,2-dimethyl-3-oxopropanoate in iodobenzene (160 mg, 0.478 mmol) and sodium triacetoxyborohydride (118 mg, 0.558 mmol), and the reaction mixture was stirred for 18 h. Additional methyl 2,2-dimethyl-3-oxopropanoate in iodobenzene (320 mg) and sodium triacetoxyborohydride (236 mg) were added and the mixture was stirred at rt for 2 h. The mixture was quenched with water (2 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was dissolved in methanol (2.000 mL) and sodium hydroxide (3M, 0.664 mL, 1.992 mmol) was added. The mixture was stirred at rt for 18 h and concentrated. The residue was treated with methanol and filtered. The filtrate was purified using reverse-phase HPLC under the acidic conditions. The resulting TFA salt was treated with ACN (1 mL) and 1N HCl aqueous solution and concentrated to give 64 mg of product as off-white solid (HCl salt). MS: (M+H)+=311.4. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.19-1.34 (m, 7H), 1.59-1.83 (m, 3H), 1.98 (br. s., 3H), 2.58-2.74 (m, 1H), 2.85-3.24 (m, 7H), 3.42 (br. s., 2H), 7.08-7.43 (m, 5H).

Aufarbeitung

  1. stirringthe mixture was stirred at rt for 2 h
  2. customThe mixture was quenched with water (2 mL)
  3. extractionextracted with DCM (3×)
  4. dry with materialThe extract was dried (Na2SO4)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in methanol (2.000 mL)
  7. stirringThe mixture was stirred at rt for 18 h
  8. concentrationconcentrated
  9. additionThe residue was treated with methanol
  10. filtrationfiltered
  11. customThe filtrate was purified
  12. additionThe resulting TFA salt was treated with ACN (1 mL) and 1N HCl aqueous solution
  13. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-28b395a353a443aaad24367e8a47b0ab
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08853408B2

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