tert-Butyl propiolate → HCID 86678444, compound

HRID 1625536Notes

Reaction equation

HRID 1625536 reaction equation
[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[C:2]#[CH:3].C([N-]C(C)C)(C)C.[Li+].C([O-])(=O)C#C.[Li+].[C:24]([O:28][C:29]([N:31]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C@@H:32]([CH2:40][CH2:41][CH:42]=[O:43])[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:30])([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[C:47]([O:46][C:44]([N:31]([C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:30])[C@H:32]([C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:40][CH2:41][CH:42]([OH:43])[C:3]#[C:2][C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])=[O:45])([CH3:50])([CH3:48])[CH3:49]

Participants

6

Reactant 4

HCID 543038tert-Butyl propiolateHCID 2724682Lithium diisopropylamideHCID 10905171HCID 10905171, compoundHCID 23696940HCID 23696940, compound

Product 1

HCID 86678444HCID 86678444, compoundYield 40.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl propiolate (42.7 mg, 0.34 mmol) in a dry THF (1.5 mL) was slowly added lithium diisopropylamide (2.0 M in THF/ethyl benzene, 0.15 mL, 0.29 mmol) at −78° C. under nitrogen atmosphere. The resulting reaction mixture was continued stirring at the same temperature for 1.0 hour (to generate lithium propiolate anion), then slowly added (S)-tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-5-oxopentanoate (0.075 g, 0.193 mmol) in 1.0 mL THF solution. The mixture was stirred at the same temperature for 90 minutes (until finished by TLC). Then, the reaction was quenched with saturated aqueous NH4Cl (0.5 mL) solution and warmed to room temperature by removing the external acetone/dry ice bath. The reaction solution was diluted with ethyl acetate (20 mL) and an aqueous saturated solution of NH4Cl (15 mL) was added with stirring. The aqueous phase was extracted with ethyl acetate (50 mL) and the combined organic layers dried and concentrated under reduced pressure. The resulting residue was purified on 12 g silica gel column (eluent, hexanes to 40% ethyl acetate in hexanes) to afford (7S)-di-tert-butyl 7-(bis(tert-butoxycarbonyl)amino)-4-hydroxyoct-2-ynedioate (diastereomeric mixture, 40 mg, 40.3% yield) as an oil. 1H NMR (CDCl3) δ ppm: 4.76 (dt, J=9.2, 5.2 Hz, 1H), 4.53 (m, 1H), 2.27 (m, 1H), 2.04 (m, 1H), 1.83 (m, 2H), 1.52 (s, 18H), 1.50 (s, 9H), 1.46 (s, 9H). 13C NMR (CDCl3) δ ppm: 169.63, 169.52, 152.47, 152.40, 152.34, 84.96, 84.94, 83.63, 83.09, 83.04, 81.48, 81.46, 77.89, 77.84, 61.90, 61.37, 58.47, 58.31, 33.75, 33.70, 28.02, 27.96, 27.93, 25.13 and 24.72. MS (ESI+): 536 (M+Na)+.

Workup

  1. customat −78° C.
  2. customThe resulting reaction mixture
  3. customThen, the reaction was quenched with saturated aqueous NH4Cl (0.5 mL) solution
  4. customby removing the external acetone/dry ice bath
  5. additionThe reaction solution was diluted with ethyl acetate (20 mL)
  6. additionan aqueous saturated solution of NH4Cl (15 mL) was added
  7. stirringwith stirring
  8. extractionThe aqueous phase was extracted with ethyl acetate (50 mL)
  9. customthe combined organic layers dried
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified on 12 g silica gel column (eluent, hexanes to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-874e8d608811459093864f663a459a1b
Source dataset
uspto-grants-2014_07
Patent number
US08784774B2

Reaction notes

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