Oxygen → HCID 15541468, compound

HRID 2238253Notes

Reaction equation

HRID 2238253 reaction equation
[CH3:1][O:2][C:3](=[O:37])/[C:4](/[C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]=[C:30]3[S:34][C:33](=[O:35])[NH:32][C:31]3=[O:36])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1)=[CH:5]\[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[CH:7]=1.C([O-])=O.[NH4+].O=O.CO.C(#N)C.O>C(O)(=O)C.[Pd].C(O)=O>[CH3:1][O:2][C:3](=[O:37])/[C:4](/[C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH:30]3[S:34][C:33](=[O:35])[NH:32][C:31]3=[O:36])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1)=[CH:5]\[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[CH:7]=1

Participants

8

Reactant 4

HCID 977OxygenHCID 2723923Ammonium formateHCID 21864137Acetonitrile methanol waterHCID 86589682HCID 86589682, compound

Product 1

HCID 15541468HCID 15541468, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 284Formic AcidSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 22 (0.60 g, 1.6 mmol) in acetic acid (15 mL) was added Pd on carbon (10%, 300 mg) and ammonium formate (4.3 g, 55.8 mmol) (caution: in a large scale reaction exothermicity may be a problem; rigorous exclusion of oxygen is desirable) and heated at 120° C. for 20 h. Catalyst was filtered through a bed of Celite® and acetic acid was evaporated under reduced pressure. Water (50 mL) was added to the residue and solid separated was filtered. Pure Z-isomer was isolated by preparative HPLC using Intersil ODS-3 preparative column (250×4.6 mm, 5 μm) running at a rate of 15 mL per minute using methanol:acetonitrile:water (3:3:2) containing formic acid (0.05%): mp 65-66° C.; 1H NMR (400 MHz, DMSO-d6) δ 12.05 (br s, 1H), 7.48 (d, J=9.2 Hz, 2H), 7.29 (d, J=8.4 Hz, 2H), 7.13 (s, 1H), 7.03 (overlapped d, J=8.8 Hz, 2H), 7.01 (overlapped d, J=8.4 Hz, 2H), 6.56 (d, J=2.0 Hz, 2H), 6.49 (t, J=2.0 Hz, 1H), 4.90 (dd, J=9.2 and 4.4 Hz, 1H), 3.77 (s, 3H), 3.75 (s, 6H), 3.38 (dd, J=14.8 and 4.8 Hz, 1H) and 3.13 (dd, J=14.4 and 9.2 Hz, 1H); MS (EI) m/z 300[M]+.

Workup

  1. customin a large scale reaction exothermicity
  2. filtrationCatalyst was filtered through a bed of Celite® and acetic acid
  3. customwas evaporated under reduced pressure
  4. additionWater (50 mL) was added to the residue and solid
  5. customseparated
  6. filtrationwas filtered
  7. customPure Z-isomer was isolated by preparative HPLC

Sources & evidence

ORD record
ord-ac58c239f8a84193a7c819b6f0f90b24
Source dataset
uspto-grants-2010_05
Patent number
US07718682B2

Reaction notes

Loading…