Tetrahydrofuran → HCID 90204489, compound

HRID 1480221Notes

Reaction equation

HRID 1480221 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[CH:5]([C:7]1[N:11]=[C:10]([CH3:12])[O:9][N:8]=1)[CH3:6])[CH3:2].C1COCC1.[Li+].C[Si]([N-:24][Si](C)(C)C)(C)C.C1(P(ON)(C2C=CC=CC=2)=O)C=CC=CC=1>CN(C=O)C>[NH2:24][C:5]([C:7]1[N:11]=[C:10]([CH3:12])[O:9][N:8]=1)([CH3:6])[C:4]([O:3][CH2:1][CH3:2])=[O:13]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 2733832Lithium HexamethyldisilazideHCID 10773832HCID 10773832, compoundHCID 10955453O-(Diphenylphosphinyl)hydroxylamine

Product 1

HCID 90204489HCID 90204489, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(5-Methyl-[1,2,4]oxadiazol-3-yl)-propionic acid ethyl ester (CAN168704-76-5, 0.5 g, 2.71 mmol) in a mixture of dry THF (15 ml)/dry DMF (4 ml) cooled down to 0° C. under an argon atmosphere was slowly added LiHMDS 1.0M solution in THF (2.85 ml, 2.85 mmol). The reaction mixture was stirred at 0° C. for 30 minutes followed by addition of O-(diphenylphosphoryl)hydroxylamine (696 mg, 2.99 mmol). The resulting suspension was let to warm up to room temperature and stirred at room temperature overnight (a white suspension formed). The reaction mixture was filtered through a pad of Celite and the filter cake was washed twice with THF. The filtrate was concentrated in vacuo and the residue was dissolved in ethylacetate. The organic phase was extracted with 5 mL aqueous Na2CO3 2M. The organic phase was collected and the aqueous phase was back-extracted with ethylacetate. The combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a gradient of dichloromethane/methanol to yield the title compound (450 mg, 83%). MS (ESI, m/z): 200.2 (M+H+).

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred at room temperature overnight (a white suspension
  3. customformed)
  4. filtrationThe reaction mixture was filtered through a pad of Celite
  5. washthe filter cake was washed twice with THF
  6. concentrationThe filtrate was concentrated in vacuo
  7. dissolutionthe residue was dissolved in ethylacetate
  8. extractionThe organic phase was extracted with 5 mL aqueous Na2CO3 2M
  9. customThe organic phase was collected
  10. extractionthe aqueous phase was back-extracted with ethylacetate
  11. dry with materialThe combined organic phases were dried over sodium sulfate
  12. customevaporated down to dryness
  13. customThe crude material was purified by flash chromatography on silica eluting with a gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-d2a14f5e5de74f58ba00c3d89c1d7946
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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