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

HRID 926148노트

반응식

HRID 926148 반응식
[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]

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 54751079XPhos Palladacycle촉매HCID 962Water용매

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온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-08fec636aa0e4ad893de26e4626257ab
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284323B2

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