Tetrahydrofuran → HCID 86682291, compound

HRID 540466Notes

Reaction equation

HRID 540466 reaction equation
[Br:1]C1C=C(CC(O)=O)C=CC=1OC.[C:14](Cl)(=[O:19])C(C)(C)C.[CH2:21]([C@H:28]1C[O:31][C:30](=[O:33])[NH:29]1)[C:22]1[CH:27]=CC=C[CH:23]=1.[Li][CH2:35][CH2:36][CH2:37][CH3:38].[CH2:39]1[CH2:43]OCC1>>[Br:1][C:36]1[CH:37]=[C:38]([C@@H:21]2[C:22]([CH3:23])([CH3:27])[O:33][C:30](=[O:31])[NH:29][CH2:28]2)[CH:43]=[CH:39][C:35]=1[O:19][CH3:14]

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 62493Pivaloyl chlorideHCID 1366153-Bromo-4-methoxyphenylacetic acidHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 178418339Butyllithium

Product 1

HCID 86682291HCID 86682291, compound

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-(3-bromo-4-methoxyphenyl)acetic acid (5 g, 20.40 mmol) in 60 mL THF was added TEA (3.13 mL, 22.44 mmol), and then pivaloyl chloride (2.64 mL, 21.42 mmol) at 0° C. The resulting reaction mixture was stirred at 0° C. for 30 mins. Ice bath was replaced with dry ice acetone bath. To a separate round-bottom flask was added (S)-4-benzyl-2-oxazolidinone (3.62 g, 20.4 mmol) and 50 mL THF. To this solution was added n-BuLi (12.8 mL, 20.4 mmol, 1.6 M in hexane) dropwise via a syringe at −78° C. The resulting reaction mixture was stirred −78° C. for 5 mins. This solution was transferred to the previous flask via channular transferring. After transferring, the reaction mixture was stirred at −78° C. for 30 mins and was allowed to warm up to rt. It was quenched by addition of 100 mL brine and 100 mL water. The reaction mixture was extracted with 200 mL 30% EtOAc in hexane. The organics were dried over sodium sulfate, filtered and concentrated. Crude product was purified on a Combiflash prepacked silica gel column eluted with 5% to 35% EtOAc in hexane to give 5.7 g desired product as colorless viscous material. 1H NMR (500 MHz, CDCl3): δ 7.57 (s, 1H), 7.3 (m, 4H), 7.18 (d, J=7.3 Hz, 1H), 6.92 (d, J=8.5 Hz, 1H), 4.71 (br, 1H), 4.1-4.3 (m, 4H), 3.93 (s, 3H), 3.31 (d, J=12.9 Hz, 1H), 2.81 (dd, J=9.8, 13.2 Hz, 1H).

Workup

  1. customat 0° C
  2. customThe resulting reaction mixture
  3. customIce bath was replaced with dry ice acetone bath
  4. customThe resulting reaction mixture
  5. stirringwas stirred −78° C. for 5 mins
  6. stirringthe reaction mixture was stirred at −78° C. for 30 mins
  7. temperatureto warm up to rt
  8. customIt was quenched by addition of 100 mL brine and 100 mL water
  9. extractionThe reaction mixture was extracted with 200 mL 30% EtOAc in hexane
  10. dry with materialThe organics were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customCrude product was purified on a Combiflash prepacked silica gel column
  14. washeluted with 5% to 35% EtOAc in hexane

Sources & evidence

ORD record
ord-d35737a45ad347a1a592dc3f5708b410
Source dataset
uspto-grants-2014_10
Patent number
US08871738B2

Reaction notes

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