2,6-Lutidine → (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-chloro-6-methylpyrimidin-4-yl)oxazolidin-2-one

HRID 57354Notes

Reaction equation

HRID 57354 reaction equation
ClC(Cl)(O[C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.[C:13]([O:17][C@H:18]([CH3:31])[C@H:19]([NH:22][C:23]1[CH:28]=[C:27]([CH3:29])[N:26]=[C:25]([Cl:30])[N:24]=1)CO)([CH3:16])([CH3:15])[CH3:14].N1C(C)=CC=CC=1C>C(Cl)Cl.[Cl-].[Na+]>[C:13]([O:17][C@@H:18]([C@H:19]1[CH2:7][O:6][C:5](=[O:11])[N:22]1[C:23]1[CH:28]=[C:27]([CH3:29])[N:26]=[C:25]([Cl:30])[N:24]=1)[CH3:31])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 79372,6-LutidineHCID 94429TriphosgeneHCID 90416038(2R,3R)-3-(tert-butoxy)-2-((2-chloro-6-methylpyrimidin-4-yl)amino)butan-1-ol

Product 1

HCID 90414673(R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-chloro-6-methylpyrimidin-4-yl)oxazolidin-2-oneYield 151.4%

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Triphosgene (35 mg, 0.12 mmol, 0.4 equiv) was added to a solution of (2R,3R)-3-(tert-butoxy)-2-((2-chloro-6-methylpyrimidin-4-yl)amino)butan-1-ol (86 mg, 0.30 mmol) in DCM (3 mL) at −78° C., followed by the dropwise addition of 2,6-lutidine (0.14 mL, 1.2 mmol, 4 equiv). The solution was allowed to warm to room temperature and was then heated at 35° C. for 5 hours. The reaction was then cooled to room temperature and diluted with DCM (30 mL) and saturated aqueous sodium chloride (30 mL). The layers were separated and the organic layer was dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane) provided (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-chloro-6-methylpyrimidin-4-yl)oxazolidin-2-one (0.057 g, white solid) in 61% yield. 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 4.73 (ddd, J=8.6, 4.1, 3.0 Hz, 1H), 4.65 (dd, J=9.4, 2.9 Hz, 1H), 4.48 (m, 1H), 4.41 (m, 1H), 2.52 (s, 3H), 1.26 (s, 9H), 1.03 (d, J=6.5 Hz, 3H); MS m/z 314.1 (M+H)+; Rt-1.02 min.

Workup

  1. temperaturewas then heated at 35° C. for 5 hours
  2. temperatureThe reaction was then cooled to room temperature
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-afecba70629c4b46bd937526d5737d64
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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