Dimethyl Sulfoxide → HCID 21034346, compound

HRID 1830947Notes

Reaction equation

HRID 1830947 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH3:11][O:12][C:13]1[C:18]2[C:19](=[O:37])[N:20]3[CH2:35][C@H:34]([OH:36])[CH2:33][C@H:21]3[C:22](=[O:32])[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:17]=2[CH:16]=[CH:15][C:14]=1[O:38][CH3:39]>C(Cl)Cl.O>[CH3:11][O:12][C:13]1[C:18]2[C:19](=[O:37])[N:20]3[CH2:35][C:34](=[O:36])[CH2:33][C@H:21]3[C:22](=[O:32])[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:29])[CH3:30])[C:17]=2[CH:16]=[CH:15][C:14]=1[O:38][CH3:39]

Participants

6

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 66912359HCID 66912359, compound

Product 1

HCID 21034346HCID 21034346, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent4×

Procedure

Anhydrous DMSO (3.28 g, 41.94 mmol) in dry DCM (20 mL) was added dropwise over 5 minutes to a stirred solution of oxalyl chloride (10.48 mL of a 2 N solution in DCM, 20.97 mmol) under a nitrogen atmosphere at −50° C. After stirring for 5 minutess, a solution 173 (5.90 g, 13.98 mmol), in dry DCM (45 mL) was added dropwise over 45 minutesutes to the reaction mixture, which was then stirred for a further 45 minutesutes at −50° C. TEA (9.89 g; 97.87 mmol) was added dropwise to the mixture over 15 minutes followed by stirring for a further 15 minutes. The reaction mixture was left to warm to room temperature, diluted with H2O (150 mL) and DCM (100 mL). The organic phase was washed with 1 N HCl (2×100 mL), water (2×100 mL), brine (2×100 mL) and dried over MgSO4. Filtration and evaporation afforded the crude product (174), which was purified by flash column chromatography using 50:50 petroleum ether (40-60°):EtOAc as eluent. Evaporation of the pure fractions in vacuo afforded the product (4.33 g, 10.3 mmol, 74%). 1H NMR (270 MHz, CDCl3) δ7.30 (s, 1H, ArH), 7.24 (s, 1H, ArH), 5.60 (d, 1H, J=9.89 Hz, SEM amino acetal CH2), 4.69 (d, 1H, J=9.89 Hz, SEM amino acetal CH2), 4.62 (dd, 1H, J=9.89, 3.12 Hz, 11a), 4.26-4.19 (m, 1H, 3), 3.95 (s, 3H, Ome), 3.94 (s, 3H, OMe), 3.81-3.49 (m, 4H, SEM 1′ CH2+1+3), 2.82-2.71 (m, 1H, 1), 0.95 (t, 2H, J=2.01 Hz, SEM 2′ CH2), −0.04 (s, 9H, SEM CH3); 13C NNR (67.8 MHz, CDCl3) δ206.8, 168.8, 165.9, 152.4, 147.5, 134.0, 120.4, 111.1, 105.6, 78.2, 67.2, 56.2, 54.8, 52.3, 37.3, 18.3, −1.3.

Workup

  1. stirringwas then stirred for a further 45 minutesutes at −50° C
  2. stirringby stirring for a further 15 minutes
  3. waitThe reaction mixture was left
  4. washThe organic phase was washed with 1 N HCl (2×100 mL), water (2×100 mL), brine (2×100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and evaporation
  7. customafforded the crude product (174), which
  8. customwas purified by flash column chromatography
  9. custom50:50 petroleum ether (40-60°)
  10. customEvaporation of the pure fractions in vacuo

Sources & evidence

ORD record
ord-0ed5b8d761f445968c19a22873b7025e
Source dataset
uspto-grants-2006_06
Patent number
US07067511B2

Reaction notes

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