Diisopropylethylamine → (R)-tert-butyl 4-((1R,2R)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-2-methyl-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1499467Notes

Reaction equation

HRID 1499467 reaction equation
[O:1]=[C:2]([N:5]1[C@H:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][O:7][C:6]1=[O:17])[CH2:3][CH3:4].CCN(C(C)C)C(C)C.[CH:27]([C@H:29]1[CH2:33][O:32][C:31]([CH3:35])([CH3:34])[N:30]1[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[O:28]>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:10]([C@@H:9]1[CH2:8][O:7][C:6](=[O:17])[N:5]1[C:2](=[O:1])[C@H:3]([CH3:4])[C@H:27]([C@H:29]1[CH2:33][O:32][C:31]([CH3:35])([CH3:34])[N:30]1[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[OH:28])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1787923-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde, (R)-(+)-HCID 10966403(R)-(-)-4-Benzyl-3-propionyl-2-oxazolidinone

Product 1

HCID 11953594(R)-tert-butyl 4-((1R,2R)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-2-methyl-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-40 °C

Procedure

To a solution of (R)-3-(1-oxopropyl)-4-benzyl-2-oxazolidinone (Aldrich, 2.0 g, 8.6 mmol) in DCM (60 mL) at −40° C., a solution of TiCl4 in DCM (1.0 M, 10.0 mL, 10.0 mmol) was added. The mixture was stirred at −40° C. for 10 min., then DIPEA (3.7 mL, 21 mmol) was added. The reaction mixture was allowed to warm to 0° C. and stirred for 20 min. A solution of tert-butyl (4R)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (Aldrich, 2.0 g, 8.7 mmol) in DCM (20 mL) was then added dropwise and the resulting mixture was stirred for 1.5 h. The reaction was quenched by the addition of a saturated aq. NH4Cl and the mixture was extracted with EtOAc. The organic extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-40% EtOAc in hexanes) to give the sub-title compound as the major product (5:2) in 87% yield (3.44 g). LCMS calc. for C24H34N2NaO7 (M+Na)+: m/z=485.2. found 485.1.

Workup

  1. temperatureto warm to 0° C.
  2. stirringstirred for 20 min
  3. stirringthe resulting mixture was stirred for 1.5 h
  4. customThe reaction was quenched by the addition of a saturated aq. NH4Cl
  5. extractionthe mixture was extracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on silica gel (0-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-cd0c4e216bd645bebcfaa031f4b75a2b
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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