Lithium Chloride → HCID 11307776, compound

HRID 1003265Notes

Reaction equation

HRID 1003265 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=1I)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]([O:25][C:26]([N:28]1[CH2:37][CH2:36][CH2:35][C@:30]2([O:34][CH2:33][CH:32]=[CH:31]2)[C@@H:29]1[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:27])([CH3:24])([CH3:23])[CH3:22].[Cl-].[Li+].C([O-])=O.[K+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=1[C@H:32]1[CH2:31][C@@:30]2([CH2:35][CH2:36][CH2:37][N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[C@H:29]2[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[O:34][CH2:33]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 433294Lithium ChlorideHCID 2735122Potassium Formate2×HCID 113952781-(Benzyloxy)-2-iodo-4-(trifluoromethoxy)benzene2×HCID 11404273HCID 11404273, compound

Product 1

HCID 11307776HCID 11307776, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-benzyloxy-5-(trifluoromethoxy)iodobenzene (Description 22b, 21.8 g, 55.2 mmol), (5R,6S)-7-(tert-butoxycarbonyl)-6-phenyl-7-aza-1-oxa-spiro[4.5]dec-3-ene (Description 21, 7.0 g, 22.1 mmol), tetra-n-butylammonium chloride (6.18 g, 22.2 mmol), lithium chloride (9.35 g, 0.22 mol) and potassium formate (5.64 g, 67.0 mmol) in dimethylformamide (100 ml) was degassed with a firestone valve (x5) and purged with nitrogen. Palladium acetate (491 mg, 2.2 mmol) was added and the mixture was degassed with a firestone valve (x5). The mixture was stirred at 60° C. for 15 hours, then further 2-benzyloxy-5-(trifluoromethoxy)iodobenzene (Description 22b, 4.32 g, 11.0 mmol), potassium formate (2.78 g, 33.5 mmol) and palladium acetate 260 mg, 1.1 mmol) were added. The mixture was stirred at 60° C. for 22 hours, cooled and filtered. The solvent was evaporated under reduced pressure, water (600 ml) was added and the mixture was extracted with ethyl acetate (2×300 ml). The combined organic fractions were washed with brine (300 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/CH2Cl2 (75:25 increasing to 0:100) then CH2Cl2 /EtOAc (95:5), to give the title compound (9.42 g, 73%). 1H NMR (360 MHz, CDCl3) δ 7.56 (2H, d, J 7.7 Hz), 7.40-7.20 (8H, m), 7.14 (1H, d, J 2.0 Hz), 7.00 (1H, dd, J 8.9, 2.0 Hz), 6.88 (1H, d, J 8.9 Hz), 5.30 (1H, s), 5.08 (2H, s), 4.27 (1H, m), 3.97 (1H, m), 3.87 (2H, m), 2.78 (1H, m), 2.56 (1H, m), 2.15 (1H, m), 1.96 (1H, m), 1.67 (3H, m), and 1.42 (9H, s).

Workup

  1. customwas degassed with a firestone valve (x5)
  2. custompurged with nitrogen
  3. customthe mixture was degassed with a firestone valve (x5)
  4. stirringThe mixture was stirred at 60° C. for 22 hours
  5. temperaturecooled
  6. filtrationfiltered
  7. customThe solvent was evaporated under reduced pressure, water (600 ml)
  8. additionwas added
  9. extractionthe mixture was extracted with ethyl acetate (2×300 ml)
  10. washThe combined organic fractions were washed with brine (300 ml)
  11. dry with materialdried (MgSO4)
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was purified by flash column chromatography on silica gel
  14. washeluting with hexane/CH2Cl2 (75:25 increasing to 0:100)

Sources & evidence

ORD record
ord-1fa3f08c66624aebb853532b5f1f6bfb
Source dataset
uspto-grants-2000_04
Patent number
US06046195

Reaction notes

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