Sodium Carbonate → 5-(4-(1-methoxyethyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-one

HRID 1253951노트

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HRID 1253951 반응식
[CH3:1][N:2]1[C:6]2[CH:7]=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:9]=[CH:10][C:5]=2[O:4][C:3]1=[O:20].Br[C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:27]=1[CH:28]([O:30][CH3:31])[CH3:29].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:31][O:30][CH:28]([C:27]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[C:8]1[CH:9]=[CH:10][C:5]2[O:4][C:3](=[O:20])[N:2]([CH3:1])[C:6]=2[CH:7]=1)[CH3:29]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 595350693-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazoloneHCID 667980463-Bromo-4-(1-methoxy-ethyl)-pyridine

생성물 1

HCID 667976675-(4-(1-methoxyethyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-one수율 69%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 3-Methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3H-benzooxazol-2-one (255 mg, 0.93 mmol), 3-Bromo-4-(1-methoxy-ethyl)-pyridine (200 mg, 0.93 mmol), Na2CO3 (2 M in water, 1.6 mL, 0.8 mmol) and PdCl2(PPh3)2 (52 mg, 0.07 mmol) in DMF (3 was heated at 100″C for overnight. After concentration, the residue was diluted in DCM and saturated NH4Cl solution. After filtration and extraction, the combined extracts were dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by flash column (MeOH—CH2Cl2, v/v, 0-1.5%) to give the title compound (182 mg, 69%). The racemate was resolved by chiral HPLC (ChiralPak, IA-H column, 40% EtOH/Heptane) to the first peak (enantiomer 1, retention time=10.90 min) and the second peak (enantiomer 2, retention time 14.25 min). ESI-MS m/z: 285 [M+1]+, Retention time 1.13 min; 1HNMR (MeOD, 400 MHz) δ 1.38 (d, J=6.8 Hz, 3H), 3.30 (s, 3H), 3.48 (s, 3H), 4.69 (q, J=6.8 Hz, 1H), 7.27 (dd, J=8.0, 1.6 Hz, 1H), 7.32 (d, J=1.6 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 8.25 (d, J=6.0 Hz, 1H), 8.78 (s, 1H), 8.89 (id, J=6.0 z, 1H).

후처리

  1. temperaturewas heated at 100″C for overnight
  2. concentrationAfter concentration
  3. additionthe residue was diluted in DCM
  4. filtrationAfter filtration and extraction
  5. dry with materialthe combined extracts were dried over anhydrous Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified by flash column (MeOH—CH2Cl2, v/v, 0-1.5%)

출처 및 근거

ORD 기록
ord-b4e91ec02bd343038e18d9826fc69874
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455522B2

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