Dimethyl Sulfoxide → HCID 57066216, compound

HRID 1068245Notes

Reaction equation

HRID 1068245 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH2:12][C@@H:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH2:16][N:15]([C@@H:25]([CH:38]([CH2:41][CH3:42])[CH2:39][CH3:40])[C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)=[O:27])[CH2:14]1.C(N(CC)CC)C>C(Cl)Cl>[CH:12]([C@@H:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH2:16][N:15]([C@@H:25]([CH:38]([CH2:41][CH3:42])[CH2:39][CH3:40])[C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)=[O:27])[CH2:14]1)=[O:11]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 57162204HCID 57162204, compound

Product 1

HCID 57066216HCID 57066216, compoundYield 88.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 0.1 mL (1.15 mmol) of oxalyl chloride in 2 mL of CH2Cl2 cooled in a −78° C. bath, 0.1 mL (1.41 mmol) of dry DMSO was added. After 0.5 hr, a solution of 0.26 g (0.59 mmol) of 2(S)-(3-(R)-hydroxymethyl-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-3-ethylvaleric acid, 4-methoxybenzyl ester (step D) in 2.5 mL of CH2Cl2 was added. After 0.5 hr, 0.5 mL (3.57 mmol) of triethylamine was added to the reaction and the cold bath was removed. After stirring for 2 hr, the reaction was partitioned between water and CH2Cl2. The organic layer was washed with brine, dried and concentrated. The residue was purified on a flash column using a gradient of 20-30% EtOAc in hexane to isolate 0.23 g of the title compound. 1H NMR (CDCl3) 0.86 (m, 6H), 1.2-1.8 (m, 5H), 2.82 (m, 2H), 3.05 (t, 1H), 3.18 (m, 2H), 3.32 (d, 1H), 3.52 (m, 1H), 3.83 (s, 3H), 5.13 (s, 2H), 6.9-7.4 (m, 8H), 9.64 (d, 1H).

Workup

  1. waitAfter 0.5 hr
  2. customthe cold bath was removed
  3. customthe reaction was partitioned between water and CH2Cl2
  4. washThe organic layer was washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified on a flash column

Sources & evidence

ORD record
ord-1533483609c0443393c4fd0488c7f665
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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