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

HRID 1259832

反応式

HRID 1259832 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 according to 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, 1 eq., prepared according to WO 2007/081597) in THF (10 mL) was quickly added and the reaction proceeded 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 after standing at rt for one day (2.83 g, 75% yield). MS (ESI, m/z): 407.3 [M+H+].

後処理

  1. waitthe reaction proceeded 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-5859d27fedf84df187a55bf7c8b9fad4
出典データセット
uspto-grants-2013_06
特許番号
US08466168B2

関連ノート

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