(3S)-3-ethoxypyrrolidine → (S)-7-benzyloxy-4-(3-ethoxy-pyrrolidin-1-yl)-2-methyl-quinoline hydrochloride

HRID 2415476노트

반응식

HRID 2415476 반응식
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:20])=[CH:14][C:15]([CH3:19])=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21]([O:23][C@H:24]1[CH2:28][CH2:27][NH:26][CH2:25]1)[CH3:22]>>[ClH:20].[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([N:26]3[CH2:27][CH2:28][C@H:24]([O:23][CH2:21][CH3:22])[CH2:25]3)=[CH:14][C:15]([CH3:19])=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

3

반응물 2

HCID 11116030(3S)-3-ethoxypyrrolidineHCID 226414197-Benzyloxy-4-chloro-2-methyl-quinoline

생성물 1

HCID 69288077(S)-7-benzyloxy-4-(3-ethoxy-pyrrolidin-1-yl)-2-methyl-quinoline hydrochloride수율 71%

반응 조건

온도
80 °C

실험 절차

A mixture of 436 mg (1.5 mmol) of 7-Benzyloxy-4-chloro-2-methyl-quinoline, product of example 1d), and 1.75 g (15 mmol) of (S)-3-ethoxypyrrolidine, prepared according to Tetrahedron Lett., 1995, 2745, was heated at 80° C. (oil bath temperature) under an argon atmosphere for 18 h after which time the reaction was completed according to HPLC analysis. The excess (S)-3-ethoxy-pyrrolidine was distilled off, and the residue was partitioned between EtOAc and water. The layers were separated, the organic layer was washed with water then saturated NaCl solution, dried over magnesium sulphate and concentrated in vacuo. The residue was taken-up in MeOH (1 ml) diluted with diethyl ether (30 ml) and then treated dropwise at RT under stirring with 0.7 ml of 3N HCL in MeOH. The solvent was removed and the remaining salt triturated with diethyl ether, then filtered off by suction and dried in a high vacuum to give 425 mg (69.7%) of the (S)-7-benzyloxy-4-(3-ethoxy-pyrrolidin-1-yl)-2-methyl-quinoline hydrochloride as a light yellow solid. ISP mass spectrum, m/e: 363.2 (M+1 calculated for C23H26N2O2: 363).

후처리

  1. customprepared
  2. distillationThe excess (S)-3-ethoxy-pyrrolidine was distilled off
  3. customthe residue was partitioned between EtOAc and water
  4. customThe layers were separated
  5. washthe organic layer was washed with water
  6. dry with materialsaturated NaCl solution, dried over magnesium sulphate
  7. concentrationconcentrated in vacuo
  8. additiondiluted with diethyl ether (30 ml)
  9. additiontreated dropwise at RT
  10. customThe solvent was removed
  11. customthe remaining salt triturated with diethyl ether
  12. filtrationfiltered off by suction
  13. customdried in a high vacuum

출처 및 근거

ORD 기록
ord-802aa49cf40e4239a45cd98be260e3b2
출처 데이터셋
uspto-grants-2004_11
특허 번호
US06818767B2

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