3-Chlorophenylacetic acid → HCID 66845068, compound

HRID 1916379Notes

Reaction equation

HRID 1916379 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=O)[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.CC(C)(C)C(Cl)=O.[CH2:28]([C@@H:35]1[CH2:39][O:38][C:37](=[O:40])[NH:36]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[Li]CCCC.[O-][Mn](=O)(=O)=O.[K+]>C1COCC1>[CH2:28]([C@@H:35]1[CH2:39][O:38][C:37](=[O:40])[N:36]1[C:9](=[O:11])[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

8

Reactant 6

HCID 158793-Chlorophenylacetic acidHCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 516875Potassium PermanganateHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 178418339Butyllithium

Product 1

HCID 66845068HCID 66845068, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 1000 mL flask under N2, 2-(3-chlorophenyl)acetic acid (3.50 g, 20.51 mmol) was added to dry THF (300 mL), and the contents were cooled to 0° C. DIEA (3.93 mL, 22.6 mmol) was added to the stirring solution, followed by portionwise addition of trimethylacetyl chloride (2.60 g, 21.5 mmol). In a separate flask, (R)-4-benzyloxazolidin-2-one (3.82 g, 21.5 mmol) was added to dry THF (75 mL) and cooled to −78° C. under N2. n-BuLi (8.21 mL, 20.5 mmol) was added to this cold stirring solution, and the whole contents were stirred for 30 minutes at −78° C. This solution was then slowly added to the mixed anhydride at 0° C. The reaction was stirred for 2 hours and determined complete by TLC (25% ethyl acetate/hexanes, KMnO4 stain). The reaction was quenched with water (250 mL) and diluted with ethyl acetate (250 mL). The layers were separated, and the organics were washed with brine (100 mL), dried (MgSO4) and concentrated to an oil. The oil was purified by flash chromatography (10% ethyl acetate/hexanes to 25% ethyl acetate/hexanes) to give (R)-4-benzyl-3-(2-(3-chlorophenyl)acetyl)oxazolidin-2-one (1.99 g, 6.03 mmol, 29.4% yield). 1H NMR (400 MHz, CDCl3) 7.37-7.20 (m, 7H), 7.14 (d, J=6.64 Hz, 2H), 4.73-4.64 (m, 1H), 4.28 (dd, J1=16.00 Hz, J2=33.97 Hz, 2H), 4.22-4.16 (m, 2H), 3.27 (dd, J1=3.12 Hz, J2=13.27 Hz, 1H), 2.77 (dd, J1=9.37 Hz, J2=13.27 Hz, 1H).

Workup

  1. temperaturecooled to −78° C. under N2
  2. stirringThe reaction was stirred for 2 hours
  3. customThe reaction was quenched with water (250 mL)
  4. additiondiluted with ethyl acetate (250 mL)
  5. customThe layers were separated
  6. washthe organics were washed with brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated to an oil
  9. customThe oil was purified by flash chromatography (10% ethyl acetate/hexanes to 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-93c4acd79d9b438192f8271e3d7f35b6
Source dataset
uspto-grants-2013_12
Patent number
US08618097B2

Reaction notes

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