Propionyl chloride → HCID 86699979, compound

HRID 530544

Reaction equation

HRID 530544 reaction equation
[Li]CCCC.[CH2:6]([N:13]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:27](Cl)(=[O:30])[CH2:28][CH3:29]>C1COCC1>[CH2:20]([N:13]([CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[C@@H:14]([C:27](=[O:30])[CH2:28][CH3:29])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 3553452Ethyl 2-(dibenzylamino)acetateHCID 178418339Butyllithium

Product 1

HCID 86699979HCID 86699979, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a round bottomed flask, at −78° C., under argon atmosphere, a solution of DIPA (0.3 mL, 2.12 mmol) in dry THF (10 ml) was treated with n-BuLi (2.5 M in n-hexane, 0.776 mL, 1.94 mmol). After 30 min a solution of ethyl 2-(dibenzylamino)-acetate (0.5 g, 1.77 mmol) in dry THF (10 ml) was added dropwise via a cannula. After 15 min, propanoyl chloride (0.46 mL, 5.29 mmol) was added dropwise at −78° C. and the mixture stirred for 10 min at rt. The reaction was then quenched with H2O, and Et2O was subsequently added. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product, as an oil. Purification by column chromatography using a Teledyne ISCO apparatus, eluting with Cy:AcOEt (98:2) gave a pure compound (0.6 g), as a mixture of two tautomers (ketone:enol=ca. 85:15), as a colorless oil. MS (ESI) m/z: 340 [M−H]+; (ESI) m/z: 338 [M−H]−. 1H NMR (DMSO-d6) δ 0.90 (t, J=7.24 Hz, 3H), 1.23 (t, J=7.07 Hz, 3H), 2.53-2.61 (m, 1H), 2.69 (dq, J=7.23, 18.13 Hz, 1H), 3.72-3.88 (m, 4H), 4.12-4.22 (m, 3H), 7.11-7.47 (m, 10H) (reported data refer to the major ketone tautomer).

Workup

  1. customThe reaction was then quenched with H2O, and Et2O
  2. additionwas subsequently added
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a crude product
  8. customPurification by column chromatography
  9. washeluting with Cy

Sources & evidence

ORD record
ord-2cdaf90491804a4f8f13a5b85923553d
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Linked notes

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