Tetrahydrofuran → HCID 18416195, compound

HRID 990933Notes

Reaction equation

HRID 990933 reaction equation
[CH:1]([O:4][C:5]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]2[CH:11]=[C:10]3[N:19]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:20](=O)[CH2:21][O:22][C:9]3=[CH:8][C:7]=2[N:6]=1)([CH3:3])[CH3:2].[CH2:29]1COCC1>[CH3-].C[Al]C.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Cl-].[Ti+4]>[CH:1]([O:4][C:5]1[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[C:12]2[CH:11]=[C:10]3[N:19]([CH2:24][C:25]([F:26])([F:27])[F:28])[C:20](=[CH2:29])[CH2:21][O:22][C:9]3=[CH:8][C:7]=2[N:6]=1)([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 18416144HCID 18416144, compound

Product 1

HCID 18416195HCID 18416195, compound

Reagents, catalysts & solvents 1

HCID 91617563mu-Methylene-mu-chlorobis(eta5-2,4-cyclopentadien-1-yl)(dimethylaluminum)titaniumCatalyst

Procedure

This compound was made from General Method 14 from 7-isopropoxy-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinolin-2(3H)-one (0.689 g, 1.69 mmol), Tebbe's reagent (3.7 mL, 1.9 mmol) in 11 mL THF to afford 0.728 g of (±)-2,3-dihydro-7-isopropoxy-2-methylene-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinoline, an orange solid after filtration through silica gel. 1H NMR (400 MHz, CDCl3) δ 7.64 (broad s, 1H), 7.49 (s, 1H), 7.29 (s, 1H), 5.59 (hept, 1H, J=6.2), 4.95 (s, 2H), 4.91 (q, 2H, J=9.1), 1.58 (d, 6H, J=6.2). Subsequent treatment of the above solid (0.728 g) as described in General Method 14 with NaBH3CN (0.531 g, 8.45 mmol) and 4.2 mL acetic acid in 8.4 mL dichloroethane afforded 0.366 g (53%) of (±)-2,3-dihydro-7-isopropoxy-2-methyl-1-(2,2,2-trifluoroethyl)-9-(trifluoromethyl)-1H-[1,4]oxazino[3,2-g]quinoline, a yellow solid, after flash chromatography (hexanes:EtOAc, 9:1). Rf 0.28 (9:1 hexanes:EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.29 (s, 1H), 7.12 (s, 1H), 7.00 (s, 1H), 5.48 (hept, 1H, J=6.2), 4.26 (dd, ABX, 1H, J=10.7, 2.4), 4.16 (dd, ABX, 1H, J=10.7, 2.8), 3.97-4.07 (m, 1H), 3.77-3.87 (m, 1H), 3.61-3.68 (m, 1H), 1.38 (d, 6H, J=6.2), General Method 15: Hydrolysis of an isopropyl imino ether to a pyridone. A solution of the imino ether in a 3:1 acetic acid:concentrated HCl (0.1-0.2 M) solution was heated at 60-110° C. for 4-16 h. The solution was poured into sat'd NaHCO3 (80 mL/mmol), extracted with EtOAc (2×80 mL/mmol), washed with brine (60 mL/mmol), dried over MgSO4, filtered, concentrated, and purified as indicated.

Sources & evidence

ORD record
ord-a11baf1d698e426d84d4397d228de358
Source dataset
uspto-grants-2002_10
Patent number
US06462038B1

Reaction notes

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