Pentanoic Acid → HCID 68809240, compound

HRID 2276729Notes

Reaction equation

HRID 2276729 reaction equation
[C:1]([OH:7])(=O)[CH2:2][CH2:3][CH2:4][CH3:5].C(Cl)(=O)C(Cl)=O.[CH:14]([C@H:17]1[CH2:21][O:20][C:19](=[O:22])[NH:18]1)([CH3:16])[CH3:15].[Li]CCCC>C(Cl)Cl.CN(C=O)C.C1COCC1>[CH:14]([C@H:17]1[CH2:21][O:20][C:19](=[O:22])[N:18]1[C:1](=[O:7])[CH2:2][CH2:3][CH2:4][CH3:5])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 7991Pentanoic AcidHCID 65578Oxalyl chlorideHCID 7157133(4S)-4-(propan-2-yl)-1,3-oxazolidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 68809240HCID 68809240, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of pentanoic acid (5.98 g, 58.6 mmol) in CH2Cl2 (100 mL) and 10 drops DMF was added oxalyl chloride (5.64 mL, 64.4 mmol) dropwise over 5 min and the solution stirred for 2.75 h, at which time all bubbling subsided. The solution was concentrated in vacuo. In a separate flask, to a cold (−78° C.), stirred solution of (S)-4-isopropyloxazolidin-2-one (7.56 g, 58.6 mmol) in THF (280 mL) was added n-BuLi (2.5M in hexane, 23.42 mL, 58.6 mmol) dropwise via addition funnel over 20 min (temperature never exceeded −68° C.). After stirring 10 min, the above acid chloride dissolved in THF (50 mL) was added via addition funnel over 25 min. After the addition was complete, the reaction mixture was allowed to warm to room temperature as bath warmed and stirred overnight. The reaction was quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated to an amber oil. The residue was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 60% solvent A/B=hex/EtOAc, REDISEP® SiO2 120 g, applied as a DCM solution) to give Preparation 4A (6.51 g, 52%) as a colorless oil: 1H NMR (400 MHz, chloroform-d) δ ppm 4.44 (1H, ddd, J=8.16, 3.51, 3.39 Hz), 4.27 (1H, t, J=9.00 Hz), 4.21 (1H, dd, J=9.00, 3.01 Hz), 2.99 (1H, ddd, J=16.60, 8.50, 6.50 Hz), 2.86 (1H, ddd, J=16.60, 8.50, 6.78 Hz), 2.31-2.44 (1H, m), 1.56-1.72 (2H, m), 1.39 (2H, sxt, J=7.43 Hz), 0.94 (3H, t, J=7.28 Hz), 0.92 (3H, d, J=7.03 Hz), 0.88 (3H, d, J=6.78 Hz); HPLC: RT=2.497 min (CHROMOLITH® SpeedROD 4.6×50 mm (4 min grad) eluting with MeOH/H2O/0.1% TFA, 4 mL/min, monitoring at 220 nm).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. additiondropwise via addition funnel over 20 min (temperature never exceeded −68° C.)
  3. stirringAfter stirring 10 min
  4. additionwas added via addition funnel over 25 min
  5. additionAfter the addition
  6. temperaturewarmed
  7. stirringstirred overnight
  8. customThe reaction was quenched with water
  9. extractionextracted with EtOAc (2×)
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated to an amber oil
  14. customThe residue was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 60% solvent A/B=hex/EtOAc, REDISEP® SiO2 120 g
  15. customto give
  16. washHPLC: RT=2.497 min (CHROMOLITH® SpeedROD 4.6×50 mm (4 min grad) eluting with MeOH/H2O/0.1% TFA, 4 mL/min, monitoring at 220 nm)

Sources & evidence

ORD record
ord-adc27325b88c45c3885188c67d8d56e7
Source dataset
uspto-grants-2015_09
Patent number
US09133126B2

Reaction notes

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