Dimethyl Sulfoxide → HCID 86598720, compound

HRID 643080Notes

Reaction equation

HRID 643080 reaction equation
O[CH2:2][CH2:3][N:4]([CH2:12][C:13]1[N:14]=[C:15]([CH3:18])[S:16][CH:17]=1)C(=O)OC(C)(C)C.C(Cl)(=O)C(Cl)=O.CS(C)=O.C(N(CC)CC)C.[CH3:36][O:37][C:38](=[O:44])[C@H:39]([CH:41]([CH3:43])[CH3:42])[NH2:40].O.O.O.C([O-])(=O)C.[Na+].[BH3-]C#N.[Na+]>ClCCl.CO.O>[CH3:42][CH:41]([CH3:43])[C@H:39]([NH:40][CH2:2][CH2:3][NH:4][CH2:12][C:13]1[N:14]=[C:15]([CH3:18])[S:16][CH:17]=1)[C:38]([O:37][CH3:36])=[O:44]

Participants

10

Reactant 7

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 94285Valine methyl esterHCID 5003444Sodium cyanoborohydrideHCID 23665404Sodium Acetate TrihydrateHCID 66890987Tert-butyl 2-hydroxyethyl[(2-methyl-1,3-thiazol-4-yl)methyl]carbamate

Product 1

HCID 86598720HCID 86598720, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

A solution of the product of Example 61B (2.26 g) in dichloromethane (20 mL) was treated with oxalyl chloride (5.4 mL, 1.5 equivalents) at −78° C., and stirred for 15 min. DMSO (1.02 mL, 2 equivalents) was added dropwise at −78° C., stirred for 15 min, and quenched with triethylamine (4 mL, 4 equivalents) as the mixture warmed to 0° C. The mixture was quenched with 20% KH2PO4, and partitioned between dichloromethane and water. The organic layer was washed with brine, dried over Na2SO4, and the solvents were evaporated. To this crude product was added methanol/water (7:2), (L)-valine methyl ester (1.21 g, 1 equivalent), sodium acetate trihydrate (1.96 g, 2 equivalents), and NaCNBH3 (0.95 g, 2 equivalents) was added portionwise over 30 min. After stirring for 1 hour, the mixture was partitioned between saturatued NaHCO3, and extracted with ethyl acetate (2×). The combined organic layer was washed with brine, dried with Na2SO4, filtered, and evaporated. The residue was treated with dichloromethane/trifluoacetic acid (10 mL, 1:1), stirred at 25° C. for 2 hrs and concentrated to give the title compound isolated as the trifluoroacetic acid salt.

Workup

  1. stirringstirred for 15 min
  2. customThe mixture was quenched with 20% KH2PO4
  3. custompartitioned between dichloromethane and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvents were evaporated
  7. additionwas added portionwise over 30 min
  8. stirringAfter stirring for 1 hour
  9. customthe mixture was partitioned between saturatued NaHCO3
  10. extractionextracted with ethyl acetate (2×)
  11. washThe combined organic layer was washed with brine
  12. dry with materialdried with Na2SO4
  13. filtrationfiltered
  14. customevaporated
  15. additionThe residue was treated with dichloromethane/trifluoacetic acid (10 mL, 1:1)
  16. stirringstirred at 25° C. for 2 hrs
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-2b461df11d74493fad0d7e97c974a031
Source dataset
uspto-grants-2010_04
Patent number
US07696226B2

Reaction notes

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