Triethylamine → 1-(4(S)-benzyl-oxazolidin-2-on-3-yl)-2-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-ethanone

HRID 2299986Notes

Reaction equation

HRID 2299986 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[F:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:30]=[CH:29][C:28]([CH2:31][C:32](O)=[O:33])=[CH:27]2)=[CH:22][CH:21]=1.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:32](=[O:33])[CH2:31][C:28]1[CH:29]=[CH:30][N:26]([C:23]2[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=2)[CH:27]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 183803942-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-acetic acidHCID 178418339Butyllithium

Product 1

HCID 183412671-(4(S)-benzyl-oxazolidin-2-on-3-yl)-2-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-ethanoneYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (S)-(−)-4-benzyl-2-oxazolidinone (710 mg, 4 mmol) in dry THF (10 mL) at −78° C. was added n-butyllithium (2.5 mL of 1.6 M in hexanes). In a separate reaction vessel, to a solution of 2-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-acetic acid (920 mg, 4.2 mmol) and triethylamine (0.7 mL, 5 mmol) in dry THF (20 ml) at −78° C. was added dropwise pivaloyl chloride (0.5 mL, 4 mmol). After stirring at −78° to 0° C. over 1 hour, then recooling to −78° C., the above solution was added via cannula. The resultant mixture was allowed to warm to ambient temperature over 17 hours, then partitioned with EtOAc and aqueous NH4Cl. The separated aqueousueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to an oil, which was purified via flash column chromatography with 15-20% EtOAc/hex gradient eluant. The oily product crystallized from benzene to give 1.04 g (69%) of 1-(4(S)-benzyl-oxazolidin-2-on-3-yl)-2-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-ethanone as a solid, mp 106-8° C. 1H NMR: δ 7.36-7.25 (m, 5H), 7.17-7.07 (m, 4H), 7.04 (s, 1H), 6.98 (t, 1H, J=2.6 Hz), 6.35 (dd, 1H, J=1.8, 2.6 Hz), 4.72-4.67 (m, 1H), 4.28-4.14 (m, 4H), 3.28 (dd, 1H, J=3.3, 3.6 Hz), 2.79 (dd, 1H, J=9.4, 13.4 Hz). Anal. Calculated for C22H19N2O3F: C, 69.83; H, 5.06; N, 7.40. Found: C, 69.80; H, 5.07; N, 7.30.

Workup

  1. customIn a separate reaction vessel
  2. customrecooling to −78° C.
  3. additionthe above solution was added via cannula
  4. custompartitioned with EtOAc and aqueous NH4Cl
  5. extractionThe separated aqueousueous phase was extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to an oil, which
  9. customwas purified via flash column chromatography with 15-20% EtOAc/hex gradient eluant
  10. customThe oily product crystallized from benzene

Sources & evidence

ORD record
ord-dec9197d8fc8454eb09ffe043598ed75
Source dataset
uspto-grants-2002_12
Patent number
US06495699B2

Reaction notes

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