tert-Butyl bromoacetate → (R)-tert-butyl 3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)hex-5-enoate

HRID 1771960Notes

Reaction equation

HRID 1771960 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH2:16][CH:17]=[CH2:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]([C@H:15]([CH2:16][CH:17]=[CH2:18])[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[O:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 10491506HCID 10491506, compound

Product 1

HCID 10981603(R)-tert-butyl 3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)hex-5-enoateYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

In a 250 mL round-bottomed flask, (S)-4-benzyl-3-(pent-4-enoyl)oxazolidin-2-one, Intermediate S8A (3.35 g, 12.92 mmol) was added to THF (40 mL) to give a colorless solution. The mixture was cooled in −78° C. bath for 10 min. Sodium bis(trimethylsilyl)amide (14.21 mL, 14.21 mmol) was added slowly to the reaction mixture. The reaction mixture turned a light orange color. The reaction mixture was stirred at −78° C. for 2 h. Then tert-butyl 2-bromoacetate (5.04 g, 25.8 mmol) was added slowly. The reaction mixture was stirred at −78° C. for 3 hr. The reaction was quenched with saturated NH4Cl. The mixture was diluted with brine and extracted with Et2O. The organic layer was dried over MgSO4, filtered and concentrated to give a crude material that was purified on silica gel column (120 g ISCO) eluting with a gradient from 0-50% EtOAc/hexane. [The product showed weak UV absorption at 254 nm]. Tubes with product were collected and concentrated to afford (R)-tert-butyl 3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)hex-5-enoate, Intermediate S8B (3.2 g, 8.40 mmol, 65.0% yield) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 7.40-7.21 (m, 5H), 5.89-5.66 (m, 1H), 5.15-5.03 (m, 2H), 4.73-4.61 (m, 1H), 4.34-4.23 (m, 1H), 4.16 (d, J=5.1 Hz, 2H), 3.35 (dd, J=13.4, 3.1 Hz, 1H), 2.88-2.67 (m, 2H), 2.52-2.38 (m, 2H), 2.28-2.13 (m, 1H), 1.44 (s, 9H).

Workup

  1. customto give a colorless solution
  2. stirringThe reaction mixture was stirred at −78° C. for 3 hr
  3. customThe reaction was quenched with saturated NH4Cl
  4. additionThe mixture was diluted with brine
  5. extractionextracted with Et2O
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude material that
  10. customwas purified on silica gel column (120 g ISCO)
  11. washeluting with a gradient from 0-50% EtOAc/hexane
  12. customUV absorption at 254 nm]
  13. customTubes with product were collected
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-c2fee33481404808802c393962cb46cc
Source dataset
uspto-grants-2016_02
Patent number
US09249157B2

Reaction notes

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