Triethylamine → 3-[[4,6-Bis-(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]methylene]-N-methoxy-pyrrolidin-2-one

HRID 2226434Notes

Reaction equation

HRID 2226434 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][O:21][N:22]1[CH2:26][CH2:25][CH:24](Br)[C:23]1=[O:28].C(N(CC)CC)C.[CH3:36][C:37]([C:40]1[C:45]([OH:46])=[C:44]([C:47]([CH3:50])([CH3:49])[CH3:48])[N:43]=[C:42]([CH:51]=O)[N:41]=1)([CH3:39])[CH3:38]>C1COCC1.C(O)C>[CH3:39][C:37]([C:40]1[C:45]([OH:46])=[C:44]([C:47]([CH3:50])([CH3:49])[CH3:48])[N:43]=[C:42]([CH:51]=[C:24]2[CH2:25][CH2:26][N:22]([O:21][CH3:20])[C:23]2=[O:28])[N:41]=1)([CH3:36])[CH3:38]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 139002263-Bromo-1-methoxypyrrolidin-2-oneHCID 152948964,6-Di-tert-butyl-5-hydroxypyrimidine-2-carbaldehyde

Product 1

HCID 543671713-[[4,6-Bis-(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]methylene]-N-methoxy-pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (1.5 g, 5.7 mmol) is added to a solution of N-methoxy-3-bromopyrrolidin-2-one (Ikuta, et al. J. Med. Chem. 1984, 30, 1995) (1.0 g, 5.2 mmol) in THF (10 mL) and the mixture is warmed to reflux under an argon atmosphere for 12 hours. The reaction mixture is cooled in an ice bath and the solvent is decanted away from the resulting solid. The solid is added to a solution of triethylamine (0.93 g, 9.3 mmol) and 4,6-bis-(1,1-dimethylethyl)-5-hydroxypyrimidine-2-carboxaldehyde (0.97 g, 4.1 mmol) in ethanol (10 mL). The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere. The mixture is cooled to room temperature, the EtOH is evaporated and the residue is partitioned between 50 mL EtOAc and 50 mL H2O. The organic extract is dried over MgSO4. The solvent is evaporated and the solid is recrystallized from Et2O/hexane. Yield of 3-[[4,6-bis-(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]methylene]-N-methoxypyrrolidin-2-one=0.34 g (20%), mp 184°-186° C.

Workup

  1. temperaturethe mixture is warmed
  2. temperatureto reflux under an argon atmosphere for 12 hours
  3. temperatureThe reaction mixture is cooled in an ice bath
  4. customthe solvent is decanted away from the resulting solid
  5. temperatureThe resulting mixture is warmed
  6. temperatureto reflux for 3 hours under an argon atmosphere
  7. customthe EtOH is evaporated
  8. customthe residue is partitioned between 50 mL EtOAc and 50 mL H2O
  9. extractionThe organic extract
  10. dry with materialis dried over MgSO4
  11. customThe solvent is evaporated
  12. customthe solid is recrystallized from Et2O/hexane

Sources & evidence

ORD record
ord-6b97bb0bcd074d00a02cf36847aac033
Source dataset
uspto-grants-1994_09
Patent number
US05348957

Reaction notes

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