Diisopropylethylamine → HCID 66618389, compound

HRID 532801Notes

Reaction equation

HRID 532801 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH:33]1([CH2:36][N:37]([CH2:45]OC)[C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:35][CH2:34]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:23])[C@@H:15]([C:16]1[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=1)[CH2:45][N:37]([CH2:36][CH:33]1[CH2:34][CH2:35]1)[C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:41])[CH3:42])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 15421330(R)-4-benzyl-3-(2-(4-chlorophenyl)acetyl)oxazolidin-2-oneHCID 66618049HCID 66618049, compound

Product 1

HCID 66618389HCID 66618389, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(R)-4-Benzyl-3-(2-(4-chlorophenyl)acetyl)oxazolidin-2-one (2.0 g, 6.06 mmol) was added to a flask in DCM (75 ml) followed by TiCl4 (1.38 g, 7.28 mmol) and DIEA (0.823 g, 6.37 mmol). The reaction was allowed to stir for about 15 to about 20 minutes at −78° C. at which point tert-butyl cyclopropylmethyl(methoxymethyl)carbamate (1.57 g, 7.28 mmol) was added. The reaction allowed to stir for 5 minutes, and the −78° C. bath was replaced with a 0° C. bath. The reaction was then allowed to stir for 3 hours at room temperature. After the reaction was determined to be complete by HPLC, the reaction was cooled to 0° C. and quenched by the slow addition of aqueous NaHCO3 while stirring for 10 minutes. The organic layer was separated, and the aqueous layer was re-extracted (3×EtOAc). The combined organics were dried with MgSO4, filtered and concentrated. The crude residue was purified by column chromatography, eluting 6:1 to 2:1 hexane/EtOAc to give tert-butyl (S)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-2-(4-chlorophenyl)-3-oxopropyl(cyclopropylmethyl)carbamate (2.70 g, 87%) as light brown oil. (LCMS (APCI+) [M−Boc+H]+ 412.9; Rt: 4.42 min)

Workup

  1. additionwas added
  2. customthe −78° C. bath
  3. customwas replaced with a 0° C.
  4. stirringto stir for 3 hours at room temperature
  5. customquenched by the slow addition of aqueous NaHCO3
  6. stirringwhile stirring for 10 minutes
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was re-extracted (3×EtOAc)
  9. dry with materialThe combined organics were dried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude residue was purified by column chromatography
  13. washeluting 6:1 to 2:1 hexane/EtOAc

Sources & evidence

ORD record
ord-caaf1ad59b76435096f92aa704756fcb
Source dataset
uspto-grants-2014_10
Patent number
US08853199B2

Reaction notes

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