Diethyl methylmalonate → Diethyl 2-fluoro-2-methylmalonate

HRID 1633208

反応式

HRID 1633208 の反応式
[CH3:1][CH:2]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[H][H].[F:17]N(CC(C)(C)C)S(C1C=CC(C)=CC=1)(=O)=O>O1CCCC1.C1(C)C=CC=CC=1.CCOCC>[F:17][C:2]([CH3:1])([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:8]([O:10][CH2:11][CH3:12])=[O:9]

参加物

8

反応物 4

HCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 145159p-Tolyl-N-fluoro-N-neopentylsulfonamideHCID 178418361HCID 178418361、化合物

生成物 1

HCID 13061046Diethyl 2-fluoro-2-methylmalonate収率 53.3%

試薬・触媒・溶媒 3

HCID 1140Toluene溶媒2 回HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Diethyl 2-methylmalonate (870 mg, 860 μL, 5 mmole) was dissolved in anhydrous tetrahydrofuran (10 mL) under nitrogen. Sodium hydride (250 mg as a 60% oil dispersion, 6 mmole) was added and the mixture was stirred until hydrogen evolution ceased (about 15 minutes). The reaction mixture was diluted with toluene (20 mL) and transferred dropwise to a solution of N-fluoro-N-neopentyl-p-toluenesulfonamide (1.295 g, 5 mmole) in anhydrous toluene (10 mL) over 5 minutes. A precipitate formed during addition and the reaction temperature rose from 23° to 36°. After stirring an additional 5 minutes under nitrogen, the reaction mixture was diluted with ether (100 mL), washed with aqueous 1N oxalic acid (30 mL), 10% aqueous potassium bicarbonate (30 mL), and saturated aqueous sodium chloride (30 mL) solutions, and then dried over anhydrous magnesium sulfate. Filtration, removal of solvent under reduced pressure, and purification by flash column chromatography (silica, 1:1 methylene chloride-hexane) yielded diethyl 2-fluoro-2-methylmalonate (512 mg, 53% yield) as a colorless liquid. This material, and additional samples prepared by this procedure, were analyzed and provided the following results: IR (liquid film) γmax (cm-1) 2940 (m), 1750 (s, ester), 1440 (m), 1370 (m), 1290 (s); 1H NMR (80 MHz, CDCl3) δ1.33 (t, J=8 Hz, 6H, CH2CHHD 3), 1.81 (d, J=22.67 Hz, 3H, CH3), 4.30 (q, J=8 Hz, 4H, CH2); 19F NMR (94.1 MHz, CDCl3) -158.02 (q, J=22 Hz, 1F); HRMS (M--CH2CH3) calcd. for C6H8O3F: 147.0457; found: 147.0450; LRMS (CI) m/e 193.

後処理

  1. custom(about 15 minutes)
  2. customA precipitate formed during addition
  3. customrose from 23° to 36°
  4. washwashed with aqueous 1N oxalic acid (30 mL), 10% aqueous potassium bicarbonate (30 mL), and saturated aqueous sodium chloride (30 mL) solutions
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationFiltration, removal of solvent
  7. customunder reduced pressure, and purification by flash column chromatography (silica, 1:1 methylene chloride-hexane)

出典と根拠

ORDレコード
ord-6b635b3aa92f45c2bbdd5f9733b8c548
出典データセット
uspto-grants-1984_10
特許番号
US04479901

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