Dimethylformamide → (S)-ethyl 2-tert-butoxy-2-(6-cyano-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate

HRID 926148ノート

反応式

HRID 926148 の反応式
[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[C:20]([F:23])[C:19]2[C:14](=[CH:15][CH:16]=[C:17](Cl)[CH:18]=2)[C:13]=1[OH:25])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].[CH3:31][N:32](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[C:20]([F:23])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:31]#[N:32])[CH:18]=2)[C:13]=1[OH:25])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 3

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 89681784(S)-ethyl 2-tert-butoxy-2-(6-chloro-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate

生成物 1

HCID 89681781(S)-ethyl 2-tert-butoxy-2-(6-cyano-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate

試薬・触媒・溶媒 3

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 54751079XPhos Palladacycle触媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

A mixture of (S)-ethyl 2-tert-butoxy-2-(6-chloro-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate (0.2186 g, 0.593 mmol), zinc(II) cyanide (0.0695 g, 0.593 mmol), XPhos Palladacycle (0.044 g, 0.0593 mmol) and sodium bicarbonate (0.005 g, 0.0593 mmol) in anhydrous DMF (3.0 mL) was heated in a microwave at 100° C. for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The Combined organic layer was washed with 5% lithium chloride solution, brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 15% ethyl acetate/hexanes) to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C20H21FNO4: 358.2. Found: 357.9.

後処理

  1. extractionextracted with ethyl acetate (2×)
  2. washThe Combined organic layer was washed with 5% lithium chloride solution, brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash column chromatography (silica gel, 0 to 15% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-08fec636aa0e4ad893de26e4626257ab
出典データセット
uspto-grants-2016_03
特許番号
US09284323B2

反応ノート

読み込み中…