Diethyl Malonate → HCID 67089220, compound

HRID 2075405Notes

Reaction equation

HRID 2075405 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].F[C:15]1[CH:16]=[C:17]([C:24]2[S:28][C:27]([CH2:29][CH2:30][C@@H:31]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH2:32][C:33]3[CH:34]=[N:35][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:37][CH:38]=3)=[N:26][N:25]=2)[CH:18]=[CH:19][C:20]=1[N+:21]([O-:23])=[O:22]>C1COCC1>[C:46]([O:45][C:44]([NH:43][C@@H:31]([CH2:32][C:33]1[CH:34]=[N:35][C:36]([C:39]([F:40])([F:42])[F:41])=[CH:37][CH:38]=1)[CH2:30][CH2:29][C:27]1[S:28][C:24]([C:17]2[CH:18]=[CH:19][C:20]([N+:21]([O-:23])=[O:22])=[C:15]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH:16]=2)=[N:25][N:26]=1)=[O:50])([CH3:49])([CH3:47])[CH3:48]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 57991970HCID 57991970, compound

Product 1

HCID 67089220HCID 67089220, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 60% dispersion of sodium hydride in mineral oil (48 mg, 1263 μmol) was added to a solution of diethyl malonate (191 μL, 1263 μmol) in THF (2 mL) and the mixture was stirred at room temperature for 15 minutes. This mixture was added to a solution of tert-butyl (R)-4-(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl)-1-(6-(trifluoromethyl)pyridin-3-yl)butan-2-ylcarbamate (171 mg, 316 μmol) in THF (3 mL) and the mixture was stirred at room temperature for 4 hours. The mixture was concentrated under reduced pressure, and the residue was 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 diethyl 2-(5-(5-((R)-3-(tert-butoxycarbonylamino)-4-(6-(trifluoromethyl)pyridin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-nitrophenyl)malonate (204 mg, 95% yield) as a yellow solid. LCMS (API-ES) m/z: 703.6 (M+Na+).

Workup

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

Sources & evidence

ORD record
ord-af2f97ab1d764850acb447f316ad7995
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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