1,1'-Carbonyldiimidazole → HCID 69742350, compound

HRID 23708

Reaction equation

HRID 23708 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[CH3:13][NH:14][CH2:15][C@H:16]([C:18]1[CH:23]=[N:22][CH:21]=[CH:20][N:19]=1)[OH:17]>ClCCl>[CH3:13][N:14]1[CH2:15][C@H:16]([C:18]2[CH:23]=[N:22][CH:21]=[CH:20][N:19]=2)[O:17][C:1]1=[O:2]

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 10285809(1R)-2-(methylamino)-1-pyrazin-2-ylethanol

Product 1

HCID 69742350HCID 69742350, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The optical purity is upgraded as follows: Carbonyldiimidazole (4.26 g, 1.1 equiv., 26.2 mmol) is dissolved in dichloromethane (80 mL). To this solution is slowly added, via cannula addition, (1R)-2-(methylamino)-1-pyrazin-2-ylethanol (3.66 g, 23.9 mmol) dissolved in dichloromethane (60 mL). The reaction is stirred at room temperature for 16 h. The solvent in vacuo and purification is accomplished by silica gel column chromatography (98:2 dichloromethane-methanol, sample and silica gel loaded in dichloromethane). Any uncyclized carbamate collected off the column is dissolved in methanol, to which is added a catalytic amount of 1 M NaOH and the solution is refluxed until completely cyclized. This freshly cyclized material is then purified by column chromatography as above. The combined pure oxazolidinone fractions are then concentrated in vacuo producing an 88% yield of (5R)-3-methyl-5-pyrazin-2-yl-1,3-oxazolidin-2-one (3.77 g, 21.0 mmol) as a white solid. This material is upgraded by chiral preparative HPLC to give material with >95% ee. MP: 113.5-114.1°; 1H NMR (400 MHz, CDCl3) δ 8.84, 8.62, 8.58, 5.62, 4.02, 3.80, 2.94; 13C NMR (100 MHz, CDCl3) δ 157.4, 153.2, 144.8, 144.1, 142.7, 72.2, 51.6, 31.1. MS (CI) m/z (rel. intensity) 180 (MH+, 12), 197 (45), 180 (12), 138 (35), 137 (17), 136 (99), 122 (11), 107 (24), 96 (14), 95 (10), 58 (11); HRMS (FAB) Found 180.0781; Specific Rotation [α]D25 +20 (c 0.95, methylene chloride); Anal. Found: C, 53.38; H, 5.03; N, 23.35.

Workup

  1. customThe solvent in vacuo and purification
  2. customAny uncyclized carbamate collected off the column
  3. dissolutionis dissolved in methanol, to which
  4. additionis added a catalytic amount of 1 M NaOH
  5. temperaturethe solution is refluxed
  6. customThis freshly cyclized material is then purified by column chromatography as above
  7. concentrationThe combined pure oxazolidinone fractions are then concentrated in vacuo

Sources & evidence

ORD record
ord-7c2c99946bd94fdeb0524f593393609f
Source dataset
uspto-grants-2005_02
Patent number
US06852731B2

Linked notes

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