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

반응식

HRID 516262 반응식
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]

참가 물질

7

반응물 4

HCID 887Methanol2회HCID 5938132,4,5-TrifluorobenzonitrileHCID 23665647Potassium tert-butoxide3회HCID 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

생성물 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)-carboxylate수율 104.9%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
-30 °C

실험 절차

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.

후처리

  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))

출처 및 근거

ORD 기록
ord-f0e7665ac94f410da92775eeb880a1b3
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108977B2

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