Diisopropylethylamine → HCID 118093024, compound

HRID 708858Notes

Reaction equation

HRID 708858 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:24])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=1[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[CH2:35][O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:24])[C@H:15]([C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=1[CH3:23])[CH2:35][O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 137983Benzyl chloromethyl etherHCID 118093106(S)-4-Benzyl-3-(2-(4-bromo-2-methylphenyl)acetyl)oxazolidin-2-one

Product 1

HCID 118093024HCID 118093024, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 16C (2.0 g, 5.15 mmol) in CH2Cl2 (20 ml) was added TiCl4 (6.18 ml, 6.18 mmol) at 0° C. to form a yellow solution. DIEA (1.080 ml, 6.18 mmol) was added at 0° C. to form a blue solution. The mixture was stirred at 0° C. for 1 h. Benzyl chloromethyl ether (1.428 ml, 10.30 mmol) was added and stirring was continued for 2 h at 0° C. at which point the blue turn to brownish red solution. The reaction was quenched with water, diluted with EtOAc. The aqueous layer was extracted with EtOAc. The combined organic extracts were washed with sat. NaHCO3 and brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (0-50% ethyl acetate/hexanes). The fractions containing the product was combined, concentrated to give 16D (2.4 g, 4.72 mmol, 92% yield) as a semi solid. 1H NMR (400 MHz, chloroform-d) δ ppm 2.41 (d, J=6.05 Hz, 3H) 2.78-2.93 (m, 1H) 3.30 (d, J=13.19 Hz, 1H) 3.43-3.57 (m, 1H) 4.01-4.23 (m, 3H) 4.46-4.81 (m, 3H) 5.36-5.53 (m, 1H) 7.01-7.16 (m, 1H) 7.18-7.41 (m, 12H).

Workup

  1. customto form a yellow solution
  2. customto form a blue solution
  3. stirringstirring
  4. waitwas continued for 2 h at 0° C. at which point
  5. customThe reaction was quenched with water
  6. additiondiluted with EtOAc
  7. extractionThe aqueous layer was extracted with EtOAc
  8. washThe combined organic extracts were washed with sat. NaHCO3 and brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customThe crude product was purified by flash chromatography (0-50% ethyl acetate/hexanes)
  12. additionThe fractions containing the product
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-0df1b4357f054933994b9c860bcd5a4f
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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