Methyl formate → HCID 86010339, compound

HRID 1817733Notes

Reaction equation

HRID 1817733 reaction equation
[F:1][C:2]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([I:11])[C:3]=1[C:4]#[N:5].[Li+].CC([N-]C(C)C)C.[CH:20](OC)=[O:21]>C1COCC1>[F:1][C:2]1[C:9]([F:10])=[C:8]([CH2:20][OH:21])[CH:7]=[C:6]([I:11])[C:3]=1[C:4]#[N:5]

Participants

5

Reactant 3

HCID 7865Methyl formateHCID 2724682Lithium diisopropylamideHCID 16125375HCID 16125375, compound

Product 1

HCID 86010339HCID 86010339, compoundYield 18.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A −78° C. solution of Example 26A (5.0 g, 18.9 mmol) in THF was treated with LDA (2M in hexanes, 11.5 mL, 22.6 mmol), stirred for 1 hour at −78° C., treated with methyl formate (2.34 mL, 37.8 mmol), stirred at −78° C. for 30 minutes, warmed to 0° C. for 1 hour, quenched with saturated NH4Cl and extracted three times with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was immediately dissolved in ethanol (100 mL), cooled to 0° C., and treated portionwise with NaBH4 (1.08 g). The reaction was stirred at 0° C. for 2 hours, quenched with acetone, stirred for 5 minutes, poured into water, and extracted three times with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with 2:1 hexanes/ethyl acetate to give 1.02 g of the desired product. Rf=0.84 (ethyl acetate).

Workup

  1. stirringstirred at −78° C. for 30 minutes
  2. temperaturewarmed to 0° C. for 1 hour
  3. customquenched with saturated NH4Cl
  4. extractionextracted three times with ethyl acetate
  5. washThe combined extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was immediately dissolved in ethanol (100 mL)
  10. temperaturecooled to 0° C.
  11. additiontreated portionwise with NaBH4 (1.08 g)
  12. stirringThe reaction was stirred at 0° C. for 2 hours
  13. customquenched with acetone
  14. stirringstirred for 5 minutes
  15. additionpoured into water
  16. extractionextracted three times with ethyl acetate
  17. washThe combined extracts were washed with brine
  18. dry with materialdried (MgSO4)
  19. filtrationfiltered
  20. concentrationconcentrated
  21. customThe residue was purified by flash column chromatography on silica gel with 2:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-2024df68c6d546d98601bbc17de4320b
Source dataset
uspto-grants-2009_10
Patent number
US07598283B2

Reaction notes

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