2,6-Lutidine → HCID 90415960, compound

HRID 57366Notes

Reaction equation

HRID 57366 reaction equation
[C:1]([O:5][C@@H:6]([CH3:19])[C@H:7]([NH:10][C:11]1[C:16]([F:17])=[CH:15][N:14]=[C:13]([F:18])[N:12]=1)[CH2:8][OH:9])([CH3:4])([CH3:3])[CH3:2].Cl[C:21](Cl)([O:23]C(=O)OC(Cl)(Cl)Cl)Cl.CC1C=CC=C(C)N=1.CCOC(C)=O.CCCCCCC>C(Cl)Cl.O>[C:1]([O:5][C@H:6]([C@H:7]1[CH2:8][O:9][C:21](=[O:23])[N:10]1[C:11]1[C:16]([F:17])=[CH:15][N:14]=[C:13]([F:18])[N:12]=1)[CH3:19])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 94429TriphosgeneHCID 21899848Ethylacetate heptaneHCID 90415155(2R,3S)-3-(tert-butoxy)-2-((2,5-difluoropyrimidin-4-yl)amino)butan-1-ol

Product 1

HCID 90415960HCID 90415960, compoundYield 62.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a round bottom flask containing (2R,3S)-3-(tert-butoxy)-2-((2,5-difluoropyrimidin-4-yl)amino)butan-1-ol (1.56 g, 5.67 mmol) and a stir bar under nitrogen was added DCM (57 mL). The resulting reaction mixture cooled to −70° C. in a dry ice/acetone bath. To this cold solution was added triphosgene (0.93 g, 3.12 mmol) followed by the addition of 2,6-dimethylpyridine (2.64 ml, 22.7 mmol). The resulting reaction mixture allowed to warm to room temperature and stirred 90 hr at room temperature. The reaction mixture was then diluted with DCM and water and allowed to stir 1 hr at room temperature. The phases were then partioned and aqueous phase extracted with DCM. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (R)-4-((S)-1-(tert-butoxy)ethyl)-3-(2,5-difluoropyrimidin-4-yl)oxazolidin-2-one (0.59 g, 1.96 mmol, 35% yield) as a white crystalline. 1H NMR (400 MHz, CDCl3) δ 1.03 (s, 9H) 1.16 (d, J=6.65 Hz, 3H) 4.15 (qd, J=6.39, 1.96 Hz, 1H) 4.43-4.52 (m, 1H) 4.59-4.72 (m, 2H) 8.43 (d, J=1.57 Hz, 1H). LCMS m/z 246.0 (-t-butyl fragment) (M+H)+, Rt 0.88 min.

Workup

  1. customThe resulting reaction mixture
  2. customThe resulting reaction mixture
  3. temperatureto warm to room temperature
  4. stirringto stir 1 hr at room temperature
  5. extractionaqueous phase extracted with DCM
  6. washwashed with water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-ec5971cafd0f4c9b80d8aca3e103a4d0
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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