Sodium Carbonate → 2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-pyrazin-2-yl-benzaldehyde

HRID 225441

반응식

HRID 225441 반응식
[CH3:1][CH:2]1[O:7][CH:6]([CH3:8])[CH2:5][N:4]([C:9]2[C:16]([F:17])=[C:15]([F:18])[C:14](B3OC(C)(C)C(C)(C)O3)=[CH:13][C:10]=2[CH:11]=[O:12])[CH2:3]1.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.O.I[C:39]1[CH:44]=[N:43][CH:42]=[CH:41][N:40]=1>CCOC(C)=O.O>[CH3:8][CH:6]1[O:7][CH:2]([CH3:1])[CH2:3][N:4]([C:9]2[C:16]([F:17])=[C:15]([F:18])[C:14]([C:39]3[CH:44]=[N:43][CH:42]=[CH:41][N:40]=3)=[CH:13][C:10]=2[CH:11]=[O:12])[CH2:5]1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 642841IodopyrazineHCID 18373917Acetonitrile--water (1/1)HCID 760452232-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde

생성물 1

HCID 866144992-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-pyrazin-2-yl-benzaldehyde수율 39.5%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
85 °C

실험 절차

To a suspension of 2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (11.5 g, 29.1 mmol) and sodium carbonate (8.8 g, 83.1 mmol) in previously degassed acetonitrile/water (1/1) mixture (140 mL) was added iodopyrazine (5.7 g, 27.7 mmol) under nitrogen. Bis-(triphenylphosphine)-dichloro-palladium-(II) (758 mg, 1.08 mmol) was added at room temperature and the reaction was heated overnight at 85° C. The mixture was cooled to room temperature, diluted with EtOAc and water. The phases were separated and the aqueous phase was re-extracted with EtOAc (×2). The combined organic layers were dried over MgSO4 and concentrated to give a brown oil. Purification on silica gel (hexane/EtOAc 9/1, 8/2 then 7/3) yielded 3.65 g of an off-white solid. 1H-NMR (500 MHz, CDCl3) d 10.35 (s, 1H), 9.06 (t, 1H), 8.70 (dd, 1H), 8.57 (d, 1H) 8.32 (dd, 1H), 4.24 (m, 2H), 3.43 (dt, 2H), 3.05 (m, 2H), 1.32 (d, 6H).

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc (×2)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. customto give a brown oil
  7. customPurification on silica gel (hexane/EtOAc 9/1, 8/2

출처 및 근거

ORD 기록
ord-957aa693d47148a5b2ceebf72c6906e5
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557100B2

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