Water → HCID 69242447, compound

HRID 1394140Notes

Reaction equation

HRID 1394140 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11](O)[CH2:10][C@H:9]1[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:21]([N:23](CC)CC)C.CS(Cl)(=O)=O.O>C1COCC1.CN(C=O)C.[C-]#N.C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:21]#[N:23])[CH2:10][C@H:9]1[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 25155574HCID 25155574, compound

Product 1

HCID 69242447HCID 69242447, compound

Reagents, catalysts & solvents 3

HCID 165872Tetrabutylammonium CyanideCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of Example 39A (1.88 g, 6.6 mmol) and triethylamine (0.92 mL, 6.6 mmol) in THF (20 mL) at 0° C. under nitrogen was added methanesulfonyl chloride (1.51 g, 13.2 mmol). The mixture was allowed to warm up to room temperature and stirred for 12 hours after which it was concentrated under reduced pressure, and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×30 mL) and the combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure to provide a yellow liquid. The yellow liquid was taken up in 100 mL of dry DMF under nitrogen and tetrabutylammonium cyanide (5 g, 20 mmol) was added to the solution. The mixture was heated to 50° C. for 60 hours after which the mixture was poured into cold water and extracted with ethyl acetate (3×25 mL). The combined organic layers were dried (MgSO4), filtered, concentrated under reduced pressure and purified by flash silica gel chromatography eluting with 50% ethyl acetate/50% hexane to provide the titled compound. MS (DCI/NH3) m/e 294 (M+H)+; 1H NMR (300 MHz, CDCl3) δ ppm 1.43 (s, 5H) 1.49 (s, 4H) 1.86 (m, 2H) 1.99 (m, 2H) 2.03 (m, 1H) 2.10 (m, 2H) 3.40 (m, 2H) 3.52 (m, 2H) 3.69 (m, 1H) 4.58 (m, 1H) 4.65 (m, 1H).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customthe residue was partitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  4. dry with materialthe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto provide a yellow liquid
  8. temperatureThe mixture was heated to 50° C. for 60 hours after which the mixture
  9. extractionextracted with ethyl acetate (3×25 mL)
  10. dry with materialThe combined organic layers were dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. custompurified by flash silica gel chromatography
  14. washeluting with 50% ethyl acetate/50% hexane

Sources & evidence

ORD record
ord-e387aefda1ab4c86bc9fc56596f3f326
Source dataset
uspto-grants-2008_03
Patent number
US07348346B2

Reaction notes

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