Dimethyl Sulfoxide → HCID 86598720, compound

HRID 243594Notes

Reaction equation

HRID 243594 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 143B (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, filtered, 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 saturated NaHCO3 and extracted with ethyl acetate (2×). The combined organic layer was washed with brine, dried with Na2SO4, and evaporated. The residue was treated with dichloromethane/trifluoacetic acid (10 mL, 1:1) and stirred at 25° C. for 2 hrs and concentrated.

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. filtrationfiltered
  7. customthe solvents were evaporated
  8. additionwas added portionwise over 30 min
  9. stirringAfter stirring for 1 hour the mixture
  10. customwas partitioned between saturated NaHCO3
  11. extractionextracted with ethyl acetate (2×)
  12. washThe combined organic layer was washed with brine
  13. dry with materialdried with Na2SO4
  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-7e087acf65324b1281b990c4c9c01926
Source dataset
uspto-grants-2014_02
Patent number
US08653141B2

Reaction notes

Loading…