Oxalyl chloride → 5-cyano-4-fluoro-2-methoxy-N-(3-nitro-benzyl)-benzamide

HRID 457983

반응식

HRID 457983 반응식
[C:1]([C:3]1[C:4]([F:14])=[CH:5][C:6]([O:12][CH3:13])=[C:7]([CH:11]=1)[C:8]([OH:10])=O)#[N:2].C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.Cl.[N+:31]([C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH2:37][NH2:38])([O-:33])=[O:32]>ClCCl.CN(C=O)C>[C:1]([C:3]1[C:4]([F:14])=[CH:5][C:6]([O:12][CH3:13])=[C:7]([CH:11]=1)[C:8]([NH:38][CH2:37][C:36]1[CH:39]=[CH:40][CH:41]=[C:34]([N+:31]([O-:33])=[O:32])[CH:35]=1)=[O:10])#[N:2]

참가 물질

7

반응물 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 2724030Benzenemethanamine, 3-nitro-, hydrochloride (1:1)HCID 184682175-Cyano-4-fluoro-2-methoxy-benzoic acid

생성물 1

HCID 184681795-cyano-4-fluoro-2-methoxy-N-(3-nitro-benzyl)-benzamide수율 63%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

반응 조건

온도
40 °C

실험 절차

To a stirring slurry of 5-cyano-4-fluoro-2-methoxy-benzoic acid (1.92 g, 9.8 mmol) in dichloromethane (20 mL, 0.5 M) was added oxalyl chloride (2.57 mL, 29.5 mmol) and DMF (1 drop). The mixture was heated to 40° C. until the solution was clear (1–2 h). Next, the mixture was allowed to cool to room temperature, concentrated under reduced pressure, and then diluted with dichloromethane (20 mL, 0.5 M). To the stirring mixture at 0° C. was added diisopropylethyl amine (4.3 mL, 24.6 mmol) followed by 3-nitrobenzylamine hydrochloride salt (2.78 g, 14.8 mmol). The stirring under nitrogen, the solution was gradually warmed to room temperature and stirred overnight. The mixture was then diluted with dichloromethane and washed with 2N HCl (3×25 mL) and saturated aq NaCl (2×25 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford a yellow oil. Purification by MPLC (10–100% ethyl acetate in heptane, 23 mL/min, 75 min) provided [5-cyano-4-fluoro-2-methoxy-N-(3-nitro-benzyl)-benzamide (2.0 g, 63%) as a yellow solid: 1H NMR (DMSO-d6, 300 MHz) δ 8.55 (d, J=7.5 Hz, 1 H), 8.19 (9, 1 H), 8.15 (d, J=8.4 Hz, 1 H), 7.96 (bd s, 1 H), 7.70 (d, J=6.3 Hz, 1H), 7.54 (t, J=8.0 Hz, 5 H), 6.86 (d, J=10.5 Hz, 1 H), 4.76 (d, J=5.4 Hz, 1H), 4.07 (d, J=1.2 Hz, 3 H).

후처리

  1. custom(1–2 h)
  2. temperatureto cool to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additiondiluted with dichloromethane (20 mL, 0.5 M)
  5. temperatureThe stirring under nitrogen, the solution was gradually warmed to room temperature
  6. washwashed with 2N HCl (3×25 mL) and saturated aq NaCl (2×25 mL)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford a yellow oil
  11. customPurification by MPLC (10–100% ethyl acetate in heptane, 23 mL/min, 75 min)

출처 및 근거

ORD 기록
ord-ac8d3575f97b4a8188d98dc2da407ecb
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07189749B2

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