Tetrahydrofuran → 3-Chloro-5-[(2,6-difluoro-3-methylphenyl)oxy]benzonitrile

HRID 1875095ノート

反応式

HRID 1875095 の反応式
CC([O-])(C)C.[K+].C1COCC1.[F:12][C:13]1[C:18]([CH3:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=1[OH:21].[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[C:29](F)[CH:30]=1)[C:26]#[N:27].C1OCCOCCOCCOCCOCCOC1>CS(C)=O.C(OCC)(=O)C.O>[Cl:22][C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([O:21][C:14]2[C:15]([F:20])=[CH:16][CH:17]=[C:18]([CH3:19])[C:13]=2[F:12])[CH:30]=1)[C:26]#[N:27]

参加物

9

反応物 5

HCID 8028TetrahydrofuranHCID 2855718-Crown-6HCID 27348413-Chloro-5-fluorobenzonitrileHCID 27741522,6-Difluoro-3-methylphenolHCID 23665647Potassium tert-butoxide

生成物 1

HCID 684866063-Chloro-5-[(2,6-difluoro-3-methylphenyl)oxy]benzonitrile収率 70%

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
135 °C

実験手順

A 1M solution KOtBu in THF (4.41 mL, 4.41 mmol) was added to a solution of 2,6-difluoro-3-methylphenol (3 g, 20.82 mmol) in DMSO (10 mL) at 0° C. under an atmosphere of nitrogen. After 10 min, 3-chloro-5-fluorobenzonitrile (3.24 g, 20.82 mmol) and 18-CROWN-6 (0.550 g, 2.082 mmol) were added and the solution was heated to 135° C. After 6 h, the brown solution was cooled to RT and water (100 mL) and ethyl acetate (150 mL) were added. The organic layer was separated, washed with water (2×150 mL), brine (150 mL), dried over MgSO4, filtered and concentrated. The residue was purfied on silica gel (hexanes/ethyl acetate) to give the title compound (4.05 g, 70%) as a white solid (N4011-11-100). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.36 (t, 1H), 7.20 (t, 1H), 7.05-7.14 (m, 2H), 6.93-7.00 (m, 1H), 2.31 (s, 3H).

後処理

  1. waitAfter 6 h
  2. temperaturethe brown solution was cooled to RT
  3. customThe organic layer was separated
  4. washwashed with water (2×150 mL), brine (150 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-ac360c0e3a224d31a7faa44b95a2ea9b
出典データセット
uspto-grants-2012_11
特許番号
US08304419B2

反応ノート

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