Dimethyl Sulfoxide → HCID 90116572, compound

HRID 513363Notes

Reaction equation

HRID 513363 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][C@@H:13]1[CH2:17][C:16](/[CH:18]=[CH:19]/[CH3:20])=[CH:15][N:14]1[C:21]([C:23]1[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][Si:32]([CH:39]([CH3:41])[CH3:40])([CH:36]([CH3:38])[CH3:37])[CH:33]([CH3:35])[CH3:34])=[CH:25][C:24]=1[NH:42][C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][C:50]([NH:53][C:54](=[O:71])[C@@H:55]([NH:57][C:58](=[O:70])[C@@H:59]([NH:63][C:64](=[O:69])[O:65][CH2:66][CH:67]=[CH2:68])[CH:60]([CH3:62])[CH3:61])[CH3:56])=[CH:49][CH:48]=1)=[O:44])=[O:22].C(N(CC)CC)C>C(Cl)Cl>[OH:11][C@@H:12]1[N:42]([C:43]([O:45][CH2:46][C:47]2[CH:52]=[CH:51][C:50]([NH:53][C:54](=[O:71])[C@@H:55]([NH:57][C:58](=[O:70])[C@@H:59]([NH:63][C:64]([O:65][CH2:66][CH:67]=[CH2:68])=[O:69])[CH:60]([CH3:61])[CH3:62])[CH3:56])=[CH:49][CH:48]=2)=[O:44])[C:24]2[CH:25]=[C:26]([O:31][Si:32]([CH:39]([CH3:40])[CH3:41])([CH:36]([CH3:37])[CH3:38])[CH:33]([CH3:35])[CH3:34])[C:27]([O:29][CH3:30])=[CH:28][C:23]=2[C:21](=[O:22])[N:14]2[CH:15]=[C:16](/[CH:18]=[CH:19]/[CH3:20])[CH2:17][C@@H:13]12

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 131733282HCID 131733282, compound

Product 1

HCID 90116572HCID 90116572, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

Dry dimethyl sulfoxide (0.180 g, 2.3 mmol, 3.0 eq) was added dropwise to a solution of oxalyl chloride (0.147 g, 1.1 mmol, 1.5 eq) in DCM (10 mL) at −78° C. under an atmosphere of nitrogen. Maintaining the temperature at −78° C., after 20 minutes, a solution of the primary alcohol 15 (0.666 g, 0.77 mmol, 1.0 eq) in DCM (10 mL) was added dropwise. After a further 15 minutes, dry triethylamine (0.390 g, 3.85 mmol, 5.0 eq) was added, and the reaction mixture allowed to warm to room temperature. The reaction mixture was washed successively with cold 0.1N HCl (10 mL), saturated sodium hydrogen carbonate (10 mL) and brine (5 mL). The organic layer was then dried over MgSO4, filtered and concentrated under reduced pressure. The residue was then purified by flash chromatography (silica gel, 50/50 v/v n-hexane/EtOAc to 25/75 v/v n-hexane/EtOAc) to afford the product as a white solid (0.356 g, 54%). LC/MS (3.487 min (ES+)), m/z: 862.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.34 (br s, 1H), 7.47 (d, 2H, J=7.6 Hz), 7.17 (s, 1H), 7.14 (d, 2H, J=7.5 Hz), 6.86 (br s, 1H), 6.65 (br s, 1H), 6.42 (d, 1H, J=7.6 Hz), 6.22 (d, 1H, J=14.4 Hz), 5.80 (m, 1H), 5.40 (m, 1H), 5.53 (m, 1H), 5.32 (m, 1H), 5.21 (d, 2H, J=9.6 Hz), 5.06 (d, 1H, J=12.3 Hz), 4.90 (m, 1H), 4.58 (m, 3H), 3.98 (m, 1H), 3.84 (m, 1H), 3.81 (s, 3H), 3.50 (m, 1H), 3.05 (dd, 1H, J=16.0, 10.3 Hz), 2.76 (m, 1H), 2.15 (m, 1H), 1.80 (dd, 3H, J=6.7, 0.8 Hz), 1.44 (d, 3H, J=7.1 Hz), 1.16 (m, 3H), 1.01 (d, 18H, J=6.6 Hz), 0.96 (d, 3H, J=6.8 Hz), 0.92 (d, 3H, J=6.8 Hz).

Workup

  1. waitAfter a further 15 minutes
  2. temperatureto warm to room temperature
  3. washThe reaction mixture was washed successively with cold 0.1N HCl (10 mL), saturated sodium hydrogen carbonate (10 mL) and brine (5 mL)
  4. dry with materialThe organic layer was then dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was then purified by flash chromatography (silica gel, 50/50 v/v n-hexane/EtOAc to 25/75 v/v n-hexane/EtOAc)

Sources & evidence

ORD record
ord-c3817a82527749a28d5ffd75b20e36f2
Source dataset
uspto-grants-2015_08
Patent number
US09102704B2

Reaction notes

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