Triethylamine → ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate

HRID 226442ノート

反応式

HRID 226442 の反応式
COP([CH:7]([F:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(OC)=O.[Br-].[Mg+2].[Br-].CCN(CC)CC.[CH2:24]([N:31]1[CH2:35][CH2:34][C@@H:33]([NH:36][C:37]2[C:44]([Cl:45])=[CH:43][C:40]([CH:41]=O)=[CH:39][N:38]=2)[CH2:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1COCC1.C(OCC)(C)=O.O>[CH2:24]([N:31]1[CH2:35][CH2:34][C@@H:33]([NH:36][C:37]2[N:38]=[CH:39][C:40](/[CH:41]=[C:7](\[F:13])/[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:43][C:44]=2[Cl:45])[CH2:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 82241Magnesium BromideHCID 12696184Ethyl (dimethoxyphosphoryl)(fluoro)acetateHCID 866037486-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinaldehyde

生成物 1

HCID 86603747ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate収率 81.6%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 22728543Water ethylacetate溶媒

反応条件

温度
7.5 °C

実験手順

To a mixture of ethyl (dimethoxyphosphoryl)(fluoro)acetate (1.46 g) and magnesium bromide (1.33 g) in THF (20 ml) was added dropwise to a Et3N (0.92 ml) with stirring at 0-15° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at same condition for an hour. A solution of 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinaldehyde (1.36 g) in THF (10 ml) solution was added the above mixture and resultant mixture was stirred at 0-15° C. for 4 hours. The reaction mixture was poured into a mixture of AcOEt-H2O and the organic layer was washed with brine and dried over MgSO4— The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-n-hexane (3:7). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate (1.42 g).

後処理

  1. stirringthe reaction mixture was stirred at same condition for an hour
  2. stirringwas stirred at 0-15° C. for 4 hours
  3. washthe organic layer was washed with brine
  4. dry with materialdried over MgSO4— The solvent
  5. customwas evaporated in vacuo
  6. customthe residue was chromatographed on silicagel
  7. washeluting with AcOEt-n-hexane (3:7)
  8. additionThe eluted fractions containing the desired product
  9. customwere collected
  10. customevaporated in vacuo

出典と根拠

ORDレコード
ord-6fcebd23b8294e7dbcbcb0151c07f74e
出典データセット
uspto-grants-2009_07
特許番号
US07557127B2

反応ノート

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