Dimethyl Sulfoxide → HCID 131727743, compound

HRID 473531Notes

Reaction equation

HRID 473531 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.N#N.C(Cl)(Cl)Cl.[CH2:17]([O:57][CH:58]1[C@H:62]2[C@H:63]([O:83][Si:84]([C:87]([CH3:90])([CH3:89])[CH3:88])([CH3:86])[CH3:85])[N:64]([C:75]([O:77][CH2:78][C:79]([Cl:82])([Cl:81])[Cl:80])=[O:76])[C:65]3[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][C:66]=3[C:67](=[O:68])[N:61]2[CH2:60][C@H:59]1[OH:91])[CH2:18][CH2:19][CH2:20][CH2:21][O:22][CH:23]1[C@H:27]2[C@H:28]([O:48][Si:49]([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50])[N:29]([C:40]([O:42][CH2:43][C:44]([Cl:47])([Cl:46])[Cl:45])=[O:41])[C:30]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:31]=3[C:32](=[O:33])[N:26]2[CH2:25][C@H:24]1[OH:56]>C(Cl)Cl>[CH2:21]([O:22][CH:23]1[C@H:27]2[C@H:28]([O:48][Si:49]([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50])[N:29]([C:40]([O:42][CH2:43][C:44]([Cl:45])([Cl:47])[Cl:46])=[O:41])[C:30]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:31]=3[C:32](=[O:33])[N:26]2[CH2:25][C:24]1=[O:56])[CH2:20][CH2:19][CH2:18][CH2:17][O:57][CH:58]1[C@H:62]2[C@H:63]([O:83][Si:84]([C:87]([CH3:88])([CH3:89])[CH3:90])([CH3:85])[CH3:86])[N:64]([C:75]([O:77][CH2:78][C:79]([Cl:82])([Cl:81])[Cl:80])=[O:76])[C:65]3[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][C:66]=3[C:67](=[O:68])[N:61]2[CH2:60][C:59]1=[O:91]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 131727735HCID 131727735, compoundHCID 131727744HCID 131727744, compound

Product 1

HCID 131727743HCID 131727743, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent5×

Conditions

Temperature
-55 °C

Procedure

A solution of anhydrous DMSO (0.34 mL, 0.37 g, 4.78 mmol) in dry DCM (4 mL) was added dropwise over a period of 5 minutes to a stirred solution of oxalyl chloride (1.20 mL of a 2M solution in DCM, 2.39 mmol) under a nitrogen atmosphere at −60° C. (liq N2/CHCl3). After stirring at −55° C. for 15 minutes, a slurry of the substrate 42 (962 mg, 0.80 mmol) in dry DCM (8 mL) was added dropwise over a period of 10 minutes to the reaction mixture. After stirring for a further 1 h at −55° C., a solution of TEA (1.56 mL, 1.13 g; 11.2 mmol) in dry DCM (4 mL) was added dropwise over a period of 5 minutes to the reaction mixture. The reaction mixture was allowed to warm to 0° C. and then diluted with DCM (50 mL). The organic solution was washed with cold 1N HCl (20 mL), H2O (20 mL), brine (30 mL) and dried (MgSO4). Filtration and evaporation of the solvent in vacuo afforded the crude product which was purified by flash column chromatography (50:50 v/v Hexane/EtOAc) to afford bis-ketone 43 as a foam (550 mg, 57%): 1H NMR (400 MHz, CDCl3) δ 7.25 (s, 2H), 6.76 (s, 2H), 5.82 (d, 2H, J=9.3 Hz), 5.22 (d, 2H, J=12.0 Hz), 4.32 (d, 2H, J=20.4 Hz), 4.22 (d, 2H, J=12.0 Hz), 4.17-4.08 (m, 4H), 4.03-3.89 (m, 10H), 2.96 (dd, 2H, J=19.6, 10.2 Hz), 2.56 (dd, 2H, J=19.6, 2.8 Hz), 1.99-1.92 (m, 4H), 1.72-1.64 (m, 2H), 0.86 (s, 18H), 0.24 and 0.23 (s×2, 12H); 13C NMR (100 MHz, CDCl3) δ 207.7, 168.0, 153.8, 151.0, 149.5, 127.9, 124.4, 114.1, 110.8, 95.2, 87.5, 74.8, 68.8, 58.9, 56.2, 52.9, 40.4, 28.7, 25.6, 22.8 17.8, −4.12 and −5.31.

Workup

  1. stirringAfter stirring for a further 1 h at −55° C.
  2. temperatureto warm to 0° C.
  3. washThe organic solution was washed with cold 1N HCl (20 mL), H2O (20 mL), brine (30 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationFiltration and evaporation of the solvent in vacuo
  6. customafforded the crude product which
  7. customwas purified by flash column chromatography (50:50 v/v Hexane/EtOAc)

Sources & evidence

ORD record
ord-971b86fdcaca49c7b629e79b83abceb6
Source dataset
uspto-grants-2014_01
Patent number
US08633185B2

Reaction notes

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