Dimethyl Sulfoxide → HCID 88112403, compound

HRID 989047Notes

Reaction equation

HRID 989047 reaction equation
CS(C)=O.[C:5](Cl)(=[O:9])[C:6](Cl)=O.[C:11]([O:15][C:16](=[O:36])[C@:17]1([CH2:32][CH2:33]CO)[CH2:21][CH2:20][CH2:19][N:18]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])([CH3:14])([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:11]([O:15][C:16](=[O:36])[C@:17]1([CH2:32][CH2:33][CH2:6][CH:5]=[O:9])[CH2:21][CH2:20][CH2:19][N:18]1[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 20598817HCID 20598817, compound

Product 1

HCID 88112403HCID 88112403, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

Dry DMSO (9.90 mL, 139 mmol) was added dropwise over 5 min to a stirred cooled (−78° C.) solution of distilled oxalyl chloride (6.3 imL, 73.1 mmol) in CH2Cl2 (150 mL). After 20 min, a solution of the alcohol 5 (26.6 g, 73.1 mmol) in CH2Cl2 (50 mL) was added over 3 h. The resultant slurry was stirred for 30 min at −78° C. and then dry diisopropylethylamine (32.0 mL, 183 mmol) was injected dropwise over 3 h. Stirring was continued at −78° C. for 30 min, the cold bath removed, and after a further 30 min, H2O (100 mL) was added. The mixture was stirred for a further 10 min and the aqueous layer was extracted with CH2Cl2 (2×400 mL). The combined organic layers were washed with 10% v/v aqueous HCl (2×100 mL), saturated aqueous NaHCO3 (2×100 mL), and brine (1×100 mL), dried over MgSO4, and evaporated in vacuo. The residue (26.0 g, 98.5%) could be used without further purification or purified (1 g) by flash chromatograghy (SiO2; 2/8 EtOAc/hexane, Rƒ 0.32) to give 6 (880 mg, 88%) as a clear oil: IR (CH2Cl2 cast) 3032 (w), 2975 (m), 2880 (m), 1719 (s), 1698 (s) cm1; 1H NMR (200 MHz, CDCl3) δ 9.52 & 9.61 (t, 1H, J=2.0 Hz, CHO), 7.18-7.36 (m, 5H, Ar—H, 5.12 & 5.18 (d, 1H, J=10.0 Hz, 1×OCH2), 4.93 & 4.99 (d, 1H, J=11.5 Hz, 1×OCH2:), 3.51-3.78 (m, 1H, 1×δ-CH2), 3.32-3.48 (rn, 1H, 1×δ-CH2), 2.32-2.64 (m, 2H), 1.70-2.32 (m, 6H), 1.30 & 1.32 (s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3) δ 202.05 & 201.20, 172.61 & 172.46, 154.47 & 154.44, 136.90 & 136.89, 128.27 & 128.21, 128.08 & 127.93, 127.69 & 127.60, 81.16 & 80.99, 68.11 & 67.38, 66.96 & 66.41, 49.00 & 48.08, 39.02 & 38.63, 37.14 & 35.96, 27.42, 27.02 & 26.75, 22.82 & 22.15.

Workup

  1. stirringStirring
  2. waitwas continued at −78° C. for 30 min
  3. customthe cold bath removed
  4. waitafter a further 30 min
  5. additionH2O (100 mL) was added
  6. stirringThe mixture was stirred for a further 10 min
  7. extractionthe aqueous layer was extracted with CH2Cl2 (2×400 mL)
  8. washThe combined organic layers were washed with 10% v/v aqueous HCl (2×100 mL), saturated aqueous NaHCO3 (2×100 mL), and brine (1×100 mL)
  9. dry with materialdried over MgSO4
  10. customevaporated in vacuo
  11. customThe residue (26.0 g, 98.5%) could be used without further purification
  12. custompurified (1 g) by flash chromatograghy (SiO2; 2/8 EtOAc/hexane, Rƒ 0.32)

Sources & evidence

ORD record
ord-ad0b6d54a27a46c6b5f8a1b440668e8f
Source dataset
uspto-grants-2003_10
Patent number
US06638941B1

Reaction notes

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