Methanol → t-butyl 4-[2-(4-cyano-2-fluoro-5-methoxyphenoxy)ethyl]-5-cyclopropyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate

HRID 516262ノート

反応式

HRID 516262 の反応式
F[C:2]1[CH:9]=[C:8](F)[C:7]([F:11])=[CH:6][C:3]=1[C:4]#[N:5].[CH:12]1([C:15]2[C:25]3[CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:20][C:19]=3[CH:18]=[C:17]3[O:33][CH2:34][CH2:35][N:36]([CH2:37][CH2:38][OH:39])[C:16]=23)[CH2:14][CH2:13]1.C[C:41](C)([O-:43])C.[K+].CO>C1COCC1.C(OCC)(=O)C>[C:4]([C:3]1[C:2]([O:43][CH3:41])=[CH:9][C:8]([O:39][CH2:38][CH2:37][N:36]2[C:16]3=[C:15]([CH:12]4[CH2:13][CH2:14]4)[C:25]4[CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:20][C:19]=4[CH:18]=[C:17]3[O:33][CH2:34][CH2:35]2)=[C:7]([F:11])[CH:6]=1)#[N:5]

参加物

7

反応物 4

HCID 887Methanol2 回HCID 5938132,4,5-TrifluorobenzonitrileHCID 23665647Potassium tert-butoxide3 回HCID 66982760t-butyl 5-cyclopropyl-4-(2-hydroxyethyl)-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate

生成物 1

HCID 71280857t-butyl 4-[2-(4-cyano-2-fluoro-5-methoxyphenoxy)ethyl]-5-cyclopropyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate収率 104.9%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-30 °C

実験手順

To a solution of 210 mg of 2,4,5-trifluorobenzonitrile and 500 mg of t-butyl 5-cyclopropyl-4-(2-hydroxyethyl)-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate in 15 ml of THF was added portionwise 150 mg of potassium t-butoxide, followed by stirring at −30° C. for 2 hours. Further, to the reaction mixture was added 0.15 ml of MeOH and then 150 mg of potassium t-butoxide was added portionwise thereto, followed by elevating the temperature to −10° C. and stirring for 15 hours. Further, to the reaction mixture were added 0.15 ml of MeOH, and then 150 mg of potassium t-butoxide was added portionwise thereto, followed by elevating the temperature to 0° C. and stirring for additional 14 hours. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc)) to obtain 726 mg of t-butyl 4-[2-(4-cyano-2-fluoro-5-methoxyphenoxy)ethyl]-5-cyclopropyl-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate as a colorless viscous substance.

後処理

  1. customto −10° C.
  2. stirringstirring for 15 hours
  3. customto 0° C.
  4. stirringstirring for additional 14 hours
  5. washwashed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc))

出典と根拠

ORDレコード
ord-f0e7665ac94f410da92775eeb880a1b3
出典データセット
uspto-grants-2015_08
特許番号
US09108977B2

反応ノート

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