Sodium Carbonate → tert-butyl 4-[4-(trifluoromethoxy)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate

HRID 32387

반응식

HRID 32387 반응식
[Li+].[Cl-].FC(F)(F)S(O[C:9]1[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH:14]=1)(=O)=O.[F:24][C:25]([F:37])([F:36])[O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:24][C:25]([F:36])([F:37])[O:26][C:27]1[CH:32]=[CH:31][C:30]([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH:14]=2)=[CH:29][CH:28]=1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

생성물 1

HCID 58808083tert-butyl 4-[4-(trifluoromethoxy)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate수율 52.4%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
85 °C

실험 절차

Pd(PPh3)4 (87 mg, 0.0075 mmol), LiCl (190 mg, 4.5 mmol), tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate (0.50 g 1.5 mmol), 4-(trifluoromethoxy)phenylboronic acid (0.43 g, 2.1 mmol) and aq Na2CO3 (2 mL, 2N solution) were mixed in 5.2 mL DME and heated at 85° C. for 3 h followed by cooling to room temperature and concentrated under reduced pressure. The residue was partitioned between DCM (10 mL), aq Na2CO3 (10 mL, 2N solution) and conc NH4OH (0.6 mL). The layers were separated and the aqueous layer extracted with DCM (3×10 mL). The combined organic layers were dried (Na2SO4) and concentrated. Purification by column chromatography (SiO2, Heptane/Ethylacetate/DCM 5:1:1) gave tert-butyl 4-[4-(trifluoromethoxy)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate (0.27 g, 52%). The product and 5% Pd/C (30 mg) was mixed in MeOH (3 mL) and stirred under H2 (1 atm) for 24 h. The mixture was filtered through Celite and concentrated to give tert-butyl 4-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxylate (0.23 g, 86%). The crude product was dissolved in a mixture of TFA (2 mL) and DCM (4 mL) and stirred at RT for 2 h. The reaction mixture was concentrated and purified by preparative HPLC to give the title compound (0.14 g, 58%, three steps 26%).

후처리

  1. temperatureby cooling to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was partitioned between DCM (10 mL), aq Na2CO3 (10 mL, 2N solution) and conc NH4OH (0.6 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with DCM (3×10 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated
  8. customPurification by column chromatography (SiO2, Heptane/Ethylacetate/DCM 5:1:1)

출처 및 근거

ORD 기록
ord-912ef1d36ddc417483676f3dfd4358d0
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427631B2

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