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

HRID 2276868ノート

反応式

HRID 2276868 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

HCID 900798402-amino-3-cyclopropoxy-N-methoxy-N-methylbenzamide収率 64.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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)).

後処理

  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)

出典と根拠

ORDレコード
ord-0c64ea9750304606a5b61c99a26e0052
出典データセット
uspto-grants-2015_09
特許番号
US09133139B2

反応ノート

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