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Potassium Carbonate → (+)-4-Cyclopropyl-9-(1-(2-fluoro-4-(quinolin-7-yl)phenyl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

HRID 1525867
ノート
印刷プレビュー

反応式

HRID 1525867 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:10]2[CH2:24][CH2:23][C:13]3([O:18][CH2:17][C:16](=[O:19])[N:15]([CH:20]4[CH2:22][CH2:21]4)[CH2:14]3)[CH2:12][CH2:11]2)[CH3:9])=[C:4]([F:25])[CH:3]=1.[N:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33](B(O)O)[CH:34]=2)[CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH:20]1([N:15]2[CH2:14][C:13]3([CH2:23][CH2:24][N:10]([CH:8]([C:5]4[CH:6]=[CH:7][C:2]([C:33]5[CH:34]=[C:35]6[C:30]([CH:29]=[CH:28][CH:27]=[N:26]6)=[CH:31][CH:32]=5)=[CH:3][C:4]=4[F:25])[CH3:9])[CH2:11][CH2:12]3)[O:18][CH2:17][C:16]2=[O:19])[CH2:22][CH2:21]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 21886457Quinoline-7-boronic acidHCID 712707719-(1-(4-Bromo-2-fluorophenyl)ethyl)-4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

生成物 1

HCID 71275838(+)-4-Cyclopropyl-9-(1-(2-fluoro-4-(quinolin-7-yl)phenyl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one収率 24.8%

試薬・触媒・溶媒 2

HCID 178418807
HCID 178418807、化合物
触媒
HCID 312751,4-Dioxane溶媒

実験手順

A solution of 9-(1-(4-bromo-2-fluorophenyl)ethyl)-4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one (0.438 mmol) in 1,4-dioxane (2 mL) was treated with quinolin-7-ylboronic acid (0.481 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.022 mmol), and 2M aq potassium carbonate (1.313 mmol). The reaction vessel was purged with nitrogen and sealed, and the mixture was irradiated in a Biotage Initiator Microwave at 130° C. for 20 min. The resulting black mixture was diluted with water (50 mL) and extracted three times with dichloromethane. The aqueous layer was further diluted with brine (50 mL) and was then extracted with tetrahydrofuran. The organic layers were combined and were treated with Silicycle Si-thiol (50 mg), dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by silica gel chromatography (4-10% methanol/dichloromethane) followed by resolution of the product by chiral HPLC (Lux Cellulose-2 column, acetonitrile:methanol 85:15) afforded the title compound as a white solid (50 mg, 23%). MS(ES)+ m/e 460.2 [M+H]+, >99% ee, αD=+38 deg (c=0.02, acetonitrile:methano185:15).

後処理

  1. customThe reaction vessel was purged with nitrogen
  2. customsealed
  3. customthe mixture was irradiated in a Biotage Initiator Microwave at 130° C. for 20 min
  4. additionThe resulting black mixture was diluted with water (50 mL)
  5. extractionextracted three times with dichloromethane
  6. additionThe aqueous layer was further diluted with brine (50 mL)
  7. extractionwas then extracted with tetrahydrofuran
  8. additionwere treated with Silicycle Si-thiol (50 mg)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification of the residue by silica gel chromatography (4-10% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-a41796e6dd754116b6d304ce25d064af
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09084794B2

反応ノート

読み込み中…

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