Triethylamine → (R)-4-benzyl-3-(2-(4-cyclopropylphenyl)acetyl)oxazolidin-2-one

HRID 527233Notes

Reaction equation

HRID 527233 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=O)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.[CH2:14]([C@@H:21]1[CH2:25][O:24][C:23](=[O:26])[NH:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C>C1(C)C=CC=CC=1>[CH2:14]([C@@H:21]1[CH2:25][O:24][C:23](=[O:26])[N:22]1[C:11](=[O:13])[CH2:10][C:7]1[CH:6]=[CH:5][C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:9][CH:8]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 204905282-(4-Cyclopropylphenyl)acetic acid

Product 1

HCID 66845976(R)-4-benzyl-3-(2-(4-cyclopropylphenyl)acetyl)oxazolidin-2-oneYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

2-(4-Cyclopropylphenyl)acetic acid (2.82 g, 16.003 mmol) was combined with (R)-4-benzyloxazolidin-2-one (3.4030 g, 19.204 mmol) in toluene (14 mL). The suspension was treated with triethylamine (6.6917 mL, 48.010 mmol) and then heated to 80° C. The solution was treated dropwise with a solution of pivaloyl chloride (1.9893 mL, 16.003 mmol) in toluene (3.5 mL). The reaction was heated overnight at 80° C. The reaction was cooled and washed with 2N HCl and then separated. The aqueous layer was washed with toluene, and the combined organics were then washed with 2N HCl, water, saturated NaHCO3 (2×), saturated NaCl, dried over Na2SO4 and concentrated in vacuo. The crude product was subjected to chromatography on SiO2 eluting with 9:1 hexanes/ethyl acetate to yield (R)-4-benzyl-3-(2-(4-cyclopropylphenyl)acetyl)oxazolidin-2-one (3.43 g, 64%). 1H NMR (CDCl3, 400 MHz) □ 7.33-7.20 (m, 5H), 7.16-7.11 (m, 2H), 7.05 (d, J=8.2, 2H), 4.70-4.63 (m, 1H), 4.32-4.14 (m, 4H), 3.26 (dd, J1=3.2, J2=13.3, 1H), 2.75 (dd, J1=9.5, J2=13.3, 1H), 1.93-1.85 (m, 1H), 0.98-0.92 (m, 2H), 0.72-0.66 (m, 2H).

Workup

  1. temperatureThe reaction was heated overnight at 80° C
  2. temperatureThe reaction was cooled
  3. washwashed with 2N HCl
  4. customseparated
  5. washThe aqueous layer was washed with toluene
  6. washthe combined organics were then washed with 2N HCl, water, saturated NaHCO3 (2×), saturated NaCl
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f5658b1a065a45d59f1aa7996f046eca
Source dataset
uspto-grants-2016_05
Patent number
US09346789B2

Reaction notes

Loading…