Acetic Anhydride → 2-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamide

HRID 601967Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 601967
C([N:8](CC1C=CC=CC=1)[CH:9]([CH2:22][O:23][CH:24]([F:26])[F:25])[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)=[O:11])C1C=CC=CC=1.C(N(CC)CC)C.C(OC(=O)C)(=O)C>C(O)C.ClCCl.[OH-].[OH-].[Pd+2]>[NH2:8][CH:9]([CH2:22][O:23][CH:24]([F:25])[F:26])[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)=[O:11]

Komponenten

7

Edukt 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 57539235HCID 57539235, Verbindung

Produkt 1

HCID 685361582-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamideAusbeute 69,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysatorHCID 702EthanolLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

2-dibenzylamino-N-(3,4-difluoro-benzyl)-3-difluoromethoxy-propionamide (298 mg, 0.645 mmol) was stirred with 10% Pd(OH)2 (200 mg) in ethanol under H2 overnight. The reaction mixture was filtered and concentrated. The residue was mixed with triethylamine (254 mg, 2.5 mmol) in dichloromethane (2 mL) and treated with acetic anhydride (85 μL) at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was concentrated with silica gel and purified by column chromatography, eluting with 30-100% ethyl acetate in hexanes. The product was triturated with diethyl ether to give 2-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamide (125 mg, 60%) as a white solid, MP: 146° C. 1H NMR (300 MHz, CDCl3): δ(ppm) 6.92-7.16 (m, 4H), 6.47 (d, 1H), 6.25 (wt, 1H), 4.75 (m, 1H), 4.41 (m, 2H), 4.22 (dd, 1H), 4.02 (dd, 1H) and 2.05 (s, 3H).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. washwashed with water
  4. concentrationThe organic layer was concentrated with silica gel
  5. custompurified by column chromatography
  6. washeluting with 30-100% ethyl acetate in hexanes
  7. customThe product was triturated with diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-ac9bfb6e58ee4543b134e32c9af29d42
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902401B2

Notizen zur Reaktion

Wird geladen…