Diisopropylamine → (6-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-((2R,6S)-2,6-dimethylmorpholino)-3-fluoropyridin-2-yl)(1-methyl-1H-imidazol-2-yl)methanol

HRID 245396

反応式

HRID 245396 の反応式
C(NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[Si:21]([O:38][CH2:39][C:40]1[C:45]([N:46]2[CH2:51][C@H:50]([CH3:52])[O:49][C@H:48]([CH3:53])[CH2:47]2)=[C:44]([Cl:54])[C:43]([F:55])=[CH:42][N:41]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[CH3:56][N:57]1[CH:61]=[CH:60][N:59]=[C:58]1[CH:62]=[O:63]>C1COCC1>[Si:21]([O:38][CH2:39][C:40]1[N:41]=[C:42]([CH:62]([C:58]2[N:57]([CH3:56])[CH:61]=[CH:60][N:59]=2)[OH:63])[C:43]([F:55])=[C:44]([Cl:54])[C:45]=1[N:46]1[CH2:51][C@H:50]([CH3:52])[O:49][C@H:48]([CH3:53])[CH2:47]1)([C:34]([CH3:37])([CH3:35])[CH3:36])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

参加物

7

反応物 5

HCID 7912DiisopropylamineHCID 1395751-Methyl-2-imidazolecarboxaldehydeHCID 2724682Lithium diisopropylamideHCID 67319975(2R,6S)-4-(2-((tert-Butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine2 回HCID 178418339Butyllithium

生成物 1

HCID 67357736(6-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-((2R,6S)-2,6-dimethylmorpholino)-3-fluoropyridin-2-yl)(1-methyl-1H-imidazol-2-yl)methanol収率 66%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

Diisopropylamine (0.868 mL, 6.14 mmol) was added dropwise to a stirring solution of 2.5M butyllithium in hexanes (2.339 mL, 5.85 mmol) in THF (20 mL) at −78° C. The solution was warmed to 0° C. for 10 minutes and then cooled again to −78° C. Cannulation of the LDA at −78° C. into (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 45, 1.5 g, 2.92 mmol) in THF (10 mL) at −78° C. Allowed dark solution to stir for 20 minutes then cannulated into a stirring solution of 1-methyl-1H-imidazole-2-carbaldehyde (0.644 g, 5.85 mmol) in THF (10 mL) at −78° C. The solution was allowed to warm to −50° C. then quenched with saturated ammonium chloride solution. The mixture was extracted with ethyl acetate and washed resulting organics with brine. After drying the organics over sodium sulfate, filtering, and evacuating the filtrate under vacuum, a crude yellow oil was obtained. The crude oil was purified on silica using 40% ethyl acetate in n-hexane to give 1.2 g (66%) of the title compound as oil.

後処理

  1. temperaturecooled again to −78° C
  2. customat −78° C.
  3. customat −78° C
  4. temperatureto warm to −50° C.
  5. customthen quenched with saturated ammonium chloride solution
  6. extractionThe mixture was extracted with ethyl acetate
  7. washwashed
  8. customresulting organics with brine
  9. dry with materialAfter drying the organics over sodium sulfate
  10. filtrationfiltering
  11. customevacuating the filtrate under vacuum
  12. customa crude yellow oil was obtained
  13. customThe crude oil was purified on silica using 40% ethyl acetate in n-hexane

出典と根拠

ORDレコード
ord-32e76ca93dc646fd8664d0a484650498
出典データセット
uspto-grants-2014_02
特許番号
US08658641B2

関連ノート

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