Water → Rac-2-(tert-butoxycarbonylamino-methyl)-3-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid ethyl ester

HRID 1801467ノート

反応式

HRID 1801467 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:11]([O:13][C:14](=[O:25])[CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH3:12].Br[CH2:27][C:28]1[C:29]([F:40])=[CH:30][CH:31]=[C:32]2[C:37]=1[N:36]=[C:35]([O:38][CH3:39])[CH:34]=[CH:33]2.O>C1COCC1.CC(=O)OCC>[CH2:11]([O:13][C:14](=[O:25])[CH:15]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:27][C:28]1[C:29]([F:40])=[CH:30][CH:31]=[C:32]2[C:37]=1[N:36]=[C:35]([O:38][CH3:39])[CH:34]=[CH:33]2)[CH3:12]

参加物

7

反応物 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 15933116Ethyl 3-{[(tert-butoxy)carbonyl]amino}propanoateHCID 66737650HCID 66737650、化合物

生成物 1

HCID 67181701Rac-2-(tert-butoxycarbonylamino-methyl)-3-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid ethyl ester収率 75%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of LiHMDS (1M, 20 mL), cooled to −78° C., was added dropwise a solution of 3-tert-butoxycarbonylamino-propionic acid ethyl ester (2.01 g, 9.26 mmol; prepared as in Tetrahedron Lett. (2003), 44(14), 2807) in THF (20 mL). The solution was stirred at the same temperature for 90 min. A solution of 8-bromomethyl-7-fluoro-2-methoxy-quinoline (2.5 g; prepared as in WO 2007/081597) in THF (10 mL) was quickly added and the reaction proceeded for 2 h, keeping the internal temperature below −50° C. Water (100 mL) and EA (200 mL) were added. The two layers were separated and the aq. layer was extracted with EA. The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by CC (Hept-EA 2:1) to afford the title intermediate as a pale yellow oil, which solidified (2.83 g, 75% yield) after standing at rt for one day.

後処理

  1. waitthe reaction proceeded for 2 h
  2. customthe internal temperature below −50° C
  3. customThe two layers were separated
  4. extractionthe aq. layer was extracted with EA
  5. washlayers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by CC (Hept-EA 2:1)

出典と根拠

ORDレコード
ord-c276b53a2bc54b6d8a5902f66bd2b4aa
出典データセット
uspto-grants-2013_01
特許番号
US08349828B2

反応ノート

読み込み中…