Dimethyl Sulfoxide → HCID 131722701, compound

HRID 1068203Notes

Reaction equation

HRID 1068203 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][CH:12]1[C@H:16]([CH2:17][OH:18])[C@@H:15]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[CH2:14][N:13]1[C@H:26]([CH2:37][CH:38]1[CH2:40][CH2:39]1)[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28].C(N(CC)CC)C>C(Cl)Cl>[CH3:11][CH:12]1[C@H:16]([CH:17]=[O:18])[C@@H:15]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[CH2:14][N:13]1[C@H:26]([CH2:37][CH:38]1[CH2:40][CH2:39]1)[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 131722700HCID 131722700, compound

Product 1

HCID 131722701HCID 131722701, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

Oxalyl chloride (0.022 mL, 0.25 mmol) was added to 5 mL of CH2Cl2 in a dry flask under nitrogen. The solution was cooled to −78° C., DMSO (0.040 mL, 0.57 mmol) was added, and the reaction mixture was stirred for 15 minutes. A solution of 2-(R)-(2-Methyl-3-(R)-hydroxymethyl-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-3-(cyclopropyl)propionic acid, benzyl ester (88 mg, 0.21 mmol, from Step C) in 0.75 mL of CH2Cl2 was added, and the reaction mixture was stirred at −78° C. for 30 min. Triethylamine (0.153 mL, 1.1 mmol) was added and the reaction mixture was warmed to room temperature, diluted with CH2Cl2 and washed twice with 1N NaOH and brine. The solution was dried over Na2SO4, filtered and concentrated to provide 54 mg (63% yield) of the title compound. 1H NMR (400 MHz, CDCl3) δ0.02-0.19 (m, 2H), 0.39-0.55 (m, 2H), 0.78-0.86 (m, 1H), 1.28 (d, 3H), 1.50-1.57 (m, 1H), 1.78-1.85 (m, 1H), 2.60-2.66 (m, 1H), 3.05-3.15 (m, 2H), 3.36-3.47 (m, 2H), 3.69-3.75 (m, 1H), 5.15-5.26 (m, 2H), 6.89-6.96 (m, 1H), 7.00-7.04 (m, 2H), 7.21-7.30 (m, 1H), 7.32-7.43 (m, 5H), 9.57 (d, 1H); ESI-MS (M+H): 410.3; HPLC A: 2.54 min.

Workup

  1. stirringthe reaction mixture was stirred at −78° C. for 30 min
  2. temperaturethe reaction mixture was warmed to room temperature
  3. washwashed twice with 1N NaOH and brine
  4. dry with materialThe solution was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a4140d10b6b14e8481057466186e79ba
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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