Methanol → 9-Chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester

HRID 357511

반응식

HRID 357511 반응식
[NH2:1][C:2]1[C:3]([C:12](=O)[CH2:13][Cl:14])=[CH:4][C:5]2[O:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.C(N(CC)CC)C.C[CH:24]([C:28](Cl)=[O:29])[C:25](Cl)=[O:26].[CH3:31][O-:32].[Na+].CO>O.C(#N)C>[CH3:31][O:32][C:28]([C:24]1[C:25](=[O:26])[NH:1][C:2]2[CH:11]=[C:6]3[O:7][CH2:8][CH2:9][O:10][C:5]3=[CH:4][C:3]=2[C:12]=1[CH2:13][Cl:14])=[O:29]

참가 물질

8

반응물 5

HCID 887MethanolHCID 8471TriethylamineHCID 102428551-(7-Amino-2,3-dihydro-1,4-benzodioxin-6-yl)-2-chloroethan-1-oneHCID 10931669MethylmalonylchlorideHCID 10942334Sodium Methoxide

생성물 1

HCID 154504599-Chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

반응 조건

온도
0 °C

실험 절차

A 4-necked 12-L round-bottom flask is equipped with a mechanical stirrer and 500-mL addition funnel. Under nitrogen, the flask is charged with 1-(7-amino-2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-chloro-ethanone (595 g, 2.61 mol), prepared as in example 13a, triethylamine (474 mL, 3.40 mol), and anhydrous acetonitrile (3.5 L). The solution is cooled to 0° C., then methyl malonyl chloride (364 mL, 3.40 mol) is added over 35 min. The cooling bath is removed and the mixture is stirred for 5 h. To the resultant slurry is added 25% sodium methoxide in methanol (596 mL, 2.61 mol) over 10 min. After being stirred at ambient temperature for 2 h, the now very thick yellow slurry is diluted with water (3 L). The precipitate is collected on a Buchner funnel and washed with water (3 L). The yellow solid is dried in vacuo. at 60° C. yielding 9-chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester as a yellow solid. This crude product is used for the next step without further purification. Recrystallization from MeOH-DMSO (1:1) gave an analytical sample: mp>300° C. (dec.). 1H NMR (DMSO-d6, 400 MHz) δ3.85 (s, 3H), 4.32 (s, 2H), 4.36 (s, 2H), 4.83 (s, 2H), 6.83 (s, 1H), 7.40 (s, 2H), 12.0 (s, 1H). Elemental analysis: Calculated for C10H10ClNO3 : C 54.29, H 3.91, N 4.52. Found: C 53.68, H 3.84, N 4.48. HRMS (EI+): Calculated for C10 H10ClNO3 : 309.0404. Found: 309.0405.

후처리

  1. customA 4-necked 12-L round-bottom flask is equipped with a mechanical stirrer and 500-mL addition funnel
  2. customThe cooling bath is removed
  3. stirringAfter being stirred at ambient temperature for 2 h
  4. customThe precipitate is collected on a Buchner funnel
  5. washwashed with water (3 L)
  6. customThe yellow solid is dried in vacuo

출처 및 근거

ORD 기록
ord-d628ede25c4e4841aee302081958464f
출처 데이터셋
uspto-grants-1998_11
특허 번호
US05840898

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