Dimethylformamide → HCID 86761703, compound

HRID 1880576Notes

Reaction equation

HRID 1880576 reaction equation
[F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16](=[CH2:20])[CH2:17][CH2:18][OH:19])[CH:11]=2)=[CH:6][CH:5]=1.[Li][O:24][C:25]([CH3:27])=[O:26].[Li+].[Cl-].[CH3:30][N:31]([CH:33]=[O:34])C>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CC([O-])=O.CC([O-])=O.[Pd+2]>[O:19]=[CH:18][CH2:17][CH:16]([C:12]1[CH:11]=[C:10]([C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:21])([F:22])[F:1])=[CH:9][CH:8]=2)[CH:15]=[CH:14][CH:13]=1)[CH2:20][C:4]1[CH:9]=[CH:8][C:7]([C:33]([NH:31][CH2:30][CH2:27][C:25]([O:24][C:12]([CH3:16])([CH3:13])[CH3:11])=[O:26])=[O:34])=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 433294Lithium ChlorideHCID 69311702HCID 69311702, compoundHCID 178506943lithium acetate

Product 1

HCID 86761703HCID 86761703, compound

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
90 °C

Procedure

A DMF solution (4 mL) containing the intermediate from Step B (453 mg, 1.47 mmol), INTERMEDIATE 1 (607 mg, 1.62 mmol), Bu4NCl (817 mg, 2.94 mmol), LiOAc (242 mg, 3.67 mmol), LiCl (62 mg, 1.47 mmol) and Pd(OAc)2 (17 mg, 0.076 mmol) was stirred overnight at 90° C. under an argon atmosphere. The solution was partitioned between water and ethyl acetate. The organic phase was washed with water (3×), brine and dried over MgSO4. The solution was filtered, concentrated and the residue purified by silica gel chromatography using a hexanes/ethyl acetate gradient to give the title compound. 1H NMR (400 MHz, CDCl3): δ 9.67 (s, 1H); 7.63 (d, J=8.2 Hz, 2H); 7.50 (d, J=8.6 Hz, 2H); 7.39-7.33 (m, 2H); 7.29-7.24 (m, 3H); 7.15-7.08 (m, 3H); 6.79 (broad s, 1H); 3.66 (q, J=5.9 Hz, 2H); 3.61-3.55 (m, 1H); 3.03-2.97 (m, 2H); 2.85-2.81 (m, 2H); 2.53 (t, J=5.9 Hz, 2H); 1.42 (s, 9H). LCMS1 4.00 min. (M+H)=500.

Workup

  1. customThe solution was partitioned between water and ethyl acetate
  2. washThe organic phase was washed with water (3×), brine
  3. dry with materialdried over MgSO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated
  6. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-93c6c42bb9cb4f81bd00d20ceeeee111
Source dataset
uspto-grants-2012_11
Patent number
US08318760B2

Reaction notes

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