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

HRID 2415476Notes

Reaction equation

HRID 2415476 reaction equation
[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

Participants

3

Reactant 2

HCID 11116030(3S)-3-ethoxypyrrolidineHCID 22641419HCID 22641419, compound

Product 1

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

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-802aa49cf40e4239a45cd98be260e3b2
Source dataset
uspto-grants-2004_11
Patent number
US06818767B2

Reaction notes

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