Hexachloroethane → (2R,6S)-4-(2-((tert-Butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine

HRID 577829

反応式

HRID 577829 の反応式
C(NC(C)C)(C)C.C([Li])CCC.[Si:13]([O:30][CH2:31][C:32]1[C:37]([N:38]2[CH2:43][C@H:42]([CH3:44])[O:41][C@H:40]([CH3:45])[CH2:39]2)=[CH:36][C:35]([F:46])=[CH:34][N:33]=1)([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl:47]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1.CCOC(C)=O>[Si:13]([O:30][CH2:31][C:32]1[C:37]([N:38]2[CH2:39][C@H:40]([CH3:45])[O:41][C@H:42]([CH3:44])[CH2:43]2)=[C:36]([Cl:47])[C:35]([F:46])=[CH:34][N:33]=1)([C:26]([CH3:27])([CH3:29])[CH3:28])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

参加物

7

反応物 4

HCID 6214HexachloroethaneHCID 7912DiisopropylamineHCID 67318917(2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine2 回HCID 178418339Butyllithium

生成物 1

HCID 67319975(2R,6S)-4-(2-((tert-Butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A solution of diisopropylamine (3.51 ml, 24.65 mmol) in THF (30 ml) was cooled in a dry ice-acetone bath. A solution of n-butyllithium (2.5 M in hexanes, 9.28 ml, 23.20 mmol) was added and the mixture was warmed to 0° C. and recooled in a dry ice-acetone bath. The solution was added to a second solution of (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 44, 6.94 g, 14.50 mmol) in THF (30 ml) cooled in a dry ice-acetone bath. The mixture was stirred for 45 minutes before the solution was transferred via cannula to a solution of hexachloroethane (2.79 ml, 24.65 mmol) in 60 ml THF also cooled in a dry ice-acetone bath. The mixture was allowed to warm to room temperature before being diluted with EtOAc and washed with water and brine. The combined aqueous layers were extracted again with EtOAc, which was washed with brine. Drying (MgSO4) of the combined EtOAc extracts and removal of solvent gave a gummy solid that was chromatographed on silica gel (50% hexanes in CH2Cl2 followed by gradient elution to 100% CH2Cl2) to afford product as an oil that slowly solidified (5.26 g yield). MS (ES) MH+: 513 for C28H34ClFN2O2Si.

後処理

  1. customrecooled in a dry ice-acetone bath
  2. temperaturecooled in a dry ice-acetone bath
  3. temperaturealso cooled in a dry ice-acetone bath
  4. temperatureto warm to room temperature
  5. washwashed with water and brine
  6. extractionThe combined aqueous layers were extracted again with EtOAc, which
  7. washwas washed with brine
  8. customDrying
  9. custom(MgSO4) of the combined EtOAc extracts and removal of solvent
  10. customgave a gummy solid
  11. customthat was chromatographed on silica gel (50% hexanes in CH2Cl2 followed by gradient elution to 100% CH2Cl2)
  12. customto afford product as an oil that
  13. custom(5.26 g yield)

出典と根拠

ORDレコード
ord-8e89534e65554a819608b34666ac1e1a
出典データセット
uspto-grants-2015_05
特許番号
US09040528B2

関連ノート

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