Dimethyl Sulfoxide → HCID 118098682, compound

HRID 708810Notes

Reaction equation

HRID 708810 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:17]2=[CH:20][C:3]=1[CH2:4][N:5]([CH3:53])[C:6](=[O:52])[C@H:7]([NH:26][C:27]1[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=1)[C:33]([N:37]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[N:32][CH:31]=[CH:30]3)[C:8]1[CH:24]=[C:23]([CH3:25])[C:11]([C@@H:12]([CH3:22])[CH2:13][O:14][C:15](=[O:21])[NH:16]2)=[CH:10][CH:9]=1.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CS(C)=O.[C]=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO>[C:48]([O:47][C:45]([N:37]([C:38]([O:39][C:40]([CH3:42])([CH3:41])[CH3:43])=[O:44])[C:33]1[C:34]2[C:29](=[CH:28][C:27]([NH:26][C@H:7]3[C:6](=[O:52])[N:5]([CH3:53])[CH2:4][C:3]4[CH:20]=[C:17]([CH:18]=[CH:19][C:2]=4[C:15]([O:14][CH3:13])=[O:21])[NH:16][C:15](=[O:21])[O:14][CH2:13][C@H:12]([CH3:22])[C:11]4[CH:10]=[CH:9][C:8]3=[CH:24][C:23]=4[CH3:25])=[CH:36][CH:35]=2)[CH:30]=[CH:31][N:32]=1)=[O:46])([CH3:50])([CH3:51])[CH3:49]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 812191,3-Bis(diphenylphosphino)propaneHCID 118098681HCID 118098681, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 118098682HCID 118098682, compoundYield 166.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a pressure flask charged with 1B (250 mg, 0.317 mmol), palladium(II) acetate (35.6 mg, 0.158 mmol), TEA (0.132 mL, 0.951 mmol) and dppp (65.4 mg, 0.158 mmol) was dissolved with DMSO (2 mL)/MeOH (1.000 mL). The resulting mixture was charged with carbon monoxide at 25 psi and then stirred at 80° C. under and atmosphere of CO overnight. Reaction mixture was cooled to rt, filtered and concentrated. The resulting residue was dissolved in EtOAc, washed with water. The aqueous layer was then back extracted. The organic layers were combined, washed with brine and dried (Na2SO4). The crude was purified on SQ16 column equilibrated with 1% MeOH in dichloromethane to give 1C (203 mg, 83% yield): MS (ESI) m/z: 768.4 [M+H]+; 1H NMR (400 MHz, MeOD) δ ppm 7.94 (1H, d, J=5.77 Hz), 7.81 (1H, d, J=8.28 Hz), 7.58 (1H, d, J=7.03 Hz), 7.49 (1H, d, J=9.03 Hz), 7.41 (1H, d, J=5.77 Hz), 7.36 (1H, d, J=7.78 Hz), 7.16 (1H, dd, J=9.16, 2.13 Hz), 7.08 (1H, s), 6.78 (1H, d, J=1.76 Hz), 6.64 (1H, dd, J=8.28, 1.76 Hz), 6.14 (1H, s), 5.54-5.66 (2H, m), 4.52 (1H, t, J=10.92 Hz), 3.85 (1H, dd, J=10.54, 4.27 Hz), 3.74 (3H, s), 3.21 (2H, d, J=1.51 Hz), 3.20 (1H, br. s.), 2.18 (3H, s), 1.21 (4H, d, J=7.03 Hz), 1.15 (19H, s).

Workup

  1. customReaction mixture
  2. temperaturewas cooled to rt
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe resulting residue was dissolved in EtOAc
  6. washwashed with water
  7. extractionThe aqueous layer was then back extracted
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. customThe crude was purified on SQ16 column

Sources & evidence

ORD record
ord-8958a7b2689b45a49b3a6ab0e057f115
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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