Triethylamine → 2-amino-3-cyclopropoxy-N-methoxy-N-methylbenzamide

HRID 2276868노트

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HRID 2276868 반응식
[NH2:1][C:2]1[C:10]([O:11][CH:12]2[CH2:14][CH2:13]2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.O.[OH:16][N:17]1[C:21]2C=CC=CC=2N=N1.[CH2:26](N(CC)CC)C>CN(C=O)C>[NH2:1][C:2]1[C:10]([O:11][CH:12]2[CH2:14][CH2:13]2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([N:17]([O:16][CH3:26])[CH3:21])=[O:6]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 722309382-Amino-3-cyclopropoxybenzoic acid

생성물 1

HCID 900798402-amino-3-cyclopropoxy-N-methoxy-N-methylbenzamide수율 64.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

In a flask at room temperature, was added 2-amino-3-cyclopropoxybenzoic acid (6.61 g, 34.2 mmol) N,O-dimethylhydroxylamine hydrochloride (10.01 g, 103 mmol), N-ethyl-N″-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.87 g, 41.1 mmol) and 1-hydroxybenzotriazole hydrate (6.29 g, 41.1 mmol) in 50 ml of DMF. To the solution was added triethylamine (19.07 mL, 137 mmol). The reaction solution was stirred at 60° C. overnight and then cooled to room temperature. The reaction mixture was partitioned between water and ethyl acetate and transferred to a separatory funnel and washed with 10% LiCl, water, and brine. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated to provide dark oil. The crude product mixture was purified via ISCO (0%-50% of EtOAC/DCM in 15 minutes, 120 g column) to give 2-amino-3-cyclopropoxy-N-methoxy-N-methylbenzamide (5.2 g, 22.01 mmol, 64.3% yield). HPLC: RT=1.975 min (H2O/MeOH with TFA, SunFire C18 3.5 μm, 2.1×30 mm, gradient=4 min, wavelength=220 nm); MS(ES):m/z=237.12 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ 7.17 (dd, J=8.0, 1.2 Hz, 1H), 7.02 (dd, J=7.9, 1.3 Hz, 1H), 6.67 (t, J=7.9 Hz, 1H), 4.78 (br. s., 2H), 3.88-3.73 (m, 1H), 3.69-3.56 (m, 3H), 3.36 (s, 3H), 0.92-0.72 (m, 4H)).

후처리

  1. temperaturecooled to room temperature
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. customtransferred to a separatory funnel
  4. washwashed with 10% LiCl, water, and brine
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto provide dark oil
  9. customThe crude product mixture was purified via ISCO (0%-50% of EtOAC/DCM in 15 minutes, 120 g column)

출처 및 근거

ORD 기록
ord-0c64ea9750304606a5b61c99a26e0052
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133139B2

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