Dimethylformamide → (S)-ethyl 2-tert-butoxy-2-(6-cyano-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

HRID 926144Notes

Reaction equation

HRID 926144 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17](Cl)[CH:18]=2)[C:13]=1[O:24][S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].[CH3:37][N:38](C=O)C>[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])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:37]#[N:38])[CH:18]=2)[C:13]=1[O:24][S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 89681783(S)-ethyl 2-tert-butoxy-2-(6-chloro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

Product 1

HCID 131735014(S)-ethyl 2-tert-butoxy-2-(6-cyano-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 54751079XPhos PalladacycleCatalyst

Conditions

Temperature
110 °C

Procedure

A mixture of (S)-ethyl 2-tert-butoxy-2-(6-chloro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate (0.546 g, 1.13 mmol), zinc(II) cyanide (0.080 g, 0.678 mmol), XPhos Palladacycle (Strem, 0.083 g, 0.113 mmol) and sodium bicarbonate (0.009 g, 0.113 mmol) in DMF (3.0 mL) was sparged with nitrogen for 5 minutes. The reaction mixture was heated in microwave at 110° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with 5% lithium chloride solution (2×), brine and dried (MgSO4) and filtered. Concentration and purification by flash column chromatography (silica gel, 0 to 10% ethyl acetate/hexanes) gave the title compound. NMR (400 MHz, CDCl3) δ 8.19 (s, H), 8.13 (d, J=8.8 Hz, H), 7.74 (s, H), 7.71 (d, J=8.8 Hz, H), 5.73 (s, H), 4.27-4.09 (m, 2H), 2.59 (s, 3H), 1.21 (s, 9H), 1.17 (t, J=7.1 Hz, 2H).

Workup

  1. customwas sparged with nitrogen for 5 minutes
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. washwashed with 5% lithium chloride solution (2×), brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationConcentration and purification by flash column chromatography (silica gel, 0 to 10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4ffe05183e484b268034dad5f785f50b
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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