Cyclopropylamine → 5-Benzyloxy-1-cyclopropyl-2-difluoromethyl-1H-pyridin-4-one
Reaction equation
[CH2:1]([O:8][C:9]1[C:10](=[O:18])[CH:11]=[C:12]([CH:15]([F:17])[F:16])O[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]1([NH2:22])[CH2:21][CH2:20]1>CO.ClCCl.CCOCC>[CH2:1]([O:8][C:9]1[C:10](=[O:18])[CH:11]=[C:12]([CH:15]([F:16])[F:17])[N:22]([CH:19]2[CH2:21][CH2:20]2)[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Procedure
A mixture of 5-benzyloxy-2-difluoromethyl-pyran-4-one (4.0 g, 15.8 mmol) and cyclopropylamine (3.6 mL, 47.5 mmol) in methanol (40 mL) was stirred at room temperature for 7.5 hrs. The reaction mixture was concentrated in vacuo to obtain an oil. The oil was diluted with dichloromethane and ether, and a solid precipitated out. The solid was collected by suction filtration to afford 1.64 g of the title compound as the first crop. The filtrate was concentrated and then purified by column chromatography using a mixture of methanol and dichloromethane (1:20, v/v) as eluant. Fractions rich in the product were pooled together and evaporated to dryness, thereby affording a second crop (2.4 g). Crops 1 and 2 were combined to give 4.0 g (87%) of the title product. HPLC purity (peak area percent) is 98.8% at λ=280 nm using HPLC Method 1 as described above. 1H NMR (400 MHz, DMSO-D6) δ (ppm): 7.57 (s, 1H), 7.21-7.48 (m, 6H, 5ArH+CF2H), 6.44 (s, 1H), 5.05 (s, 2H, OCH2), 3.50-3.56 (m, 1H), 1.10-1.16 (m, 2H, CH2), 1.05-1.09 (m, 2H, CH2).
Workup
- concentrationThe reaction mixture was concentrated in vacuo
- customto obtain an oil
- customa solid precipitated out
- filtrationThe solid was collected by suction filtration
Sources & evidence
- ORD record
- ord-1cbca6165b9c41599fc4a41b1c442baa
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673943B2
Reaction notes
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