Water → HCID 57991946, compound

HRID 2075406Notes

Reaction equation

HRID 2075406 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:37][C:38]1[CH:39]=[N:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=1)[CH2:10][CH2:11][C:12]1[S:16][C:15]([C:17]2[CH:18]=[CH:19][C:20]([N+:34]([O-:36])=[O:35])=[C:21]([CH:23](C(OCC)=O)[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:22]=2)=[N:14][N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[Cl-].[Li+]>CS(C)=O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:37][C:38]1[CH:39]=[N:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=1)[CH2:10][CH2:11][C:12]1[S:16][C:15]([C:17]2[CH:18]=[CH:19][C:20]([N+:34]([O-:36])=[O:35])=[C:21]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:22]=2)=[N:14][N:13]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 962WaterHCID 433294Lithium ChlorideHCID 67089220HCID 67089220, compound

Product 1

HCID 57991946HCID 57991946, compoundYield 79.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of diethyl 2-(5-(5-((R)-3-(tert-butoxycarbonylamino)-4-(6-(trifluoromethyl)pyridin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-nitrophenyl)malonate (165 mg, 242 μmol), water (4 μL, 242 μmol), and lithium chloride (51 mg, 1210 μmol) in DMSO (2 mL) was heated at 100° C. for 24 hours. The mixture was cooled to room temperature and partitioned between saturated aqueous NH4Cl (15 mL) and DCM (15 mL). The layers were separated, and the aqueous layer was extracted with DCM (2×15 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow solid was dissolved in MeOH/DCM, absorbed onto silica gel, and purified by flash chromatography (silica gel, 40% to 70% EtOAc/hexanes) to provide ethyl 2-(5-(5-((R)-3-(tert-butoxycarbonylamino)-4-(6-(trifluoromethyl)pyridin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-nitrophenyl)acetate (117 mg, 79%) as a white solid. LCMS (API-ES) m/z: 610.0 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between saturated aqueous NH4Cl (15 mL) and DCM (15 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (2×15 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting yellow solid was dissolved in MeOH/DCM
  8. customabsorbed onto silica gel
  9. custompurified by flash chromatography (silica gel, 40% to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fba6e003b69941be9a4fa197602ac155
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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