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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
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HRID 1525867 반응식
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
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418807
HCID 178418807, 화합물
촉매
HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-a41796e6dd754116b6d304ce25d064af
출처 데이터셋
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09084794B2

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