Hydrochloric Acid → (+/-)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-[4-(1,1,2,2-tetramethyl-1-silapropoxy)-phenyl)pyrrolidin-2-one

HRID 1837977Notes

Reaction equation

HRID 1837977 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[N:10]([CH3:11])[C:9](=[O:12])[CH2:8][C@@H:7]1[C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)=[O:5])[CH3:2].N1C=CN=C1.[CH3:25][C:26]([Si:29](Cl)([CH3:31])[CH3:30])([CH3:28])[CH3:27].Cl>CN(C=O)C>[CH2:1]([O:3][C:4]([C@@H:6]1[N:10]([CH3:11])[C:9](=[O:12])[CH2:8][C@@H:7]1[C:13]1[CH:14]=[CH:15][C:16]([O:19][Si:29]([CH3:31])([CH3:30])[C:26]([CH3:28])([CH3:27])[CH3:25])=[CH:17][CH:18]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 59066485(+/-)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-(4-hydroxyphenyl)pyrrolidin-2-one2×

Product 1

HCID 59066444(+/-)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-[4-(1,1,2,2-tetramethyl-1-silapropoxy)-phenyl)pyrrolidin-2-oneYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (±)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-(4-hydroxyphenyl)pyrrolidin-2-one (Intermediate W, 0.400 g, 1.53 mmol) in anhyd. DMF (1.5 mL) was added imidazole (0.240 g, 3.05 mmol), followed by TBDMSCl (0.250 g, 1.68 mmol) and the mixture stirred at room temperature for 18 h. The resulting mixture was poured into a 0.5N HCl solution and extracted with EtOAc. The combined organic layers were dried (MgsO4) and concentrated under reduced pressure give a clear oil which was purified by flash chromatography (gradient from 67% to 100% EtOAc/hex) to yield (±)-(4R*,5R*)-5-ethoxycarbonyl-1-methyl-4-[4-(1,1,2,2-tetramethyl-1-silapropoxy)-phenyl)pyrrolidin-2-one (512 mg, 89%) as a light yellow oil: 1H NMR (DMSO-d6) δ 0.13 (s, 6H), 0.75 (t, J=7.0 Hz, 3H), 0.91 (s, 9H), 0.24-0.70 (m, 5H), 3.55-3.76 (m, 2H), 3.88 (q, J=9.1 Hz, 1H), 4.43 (d, J=9.1 Hz, 1H), 6.75-6.79 (m, 2H), 7.07-7.13 (m, 2H).

Workup

  1. extractionextracted with EtOAc
  2. customThe combined organic layers were dried (MgsO4)
  3. concentrationconcentrated under reduced pressure
  4. customgive a clear oil which
  5. customwas purified by flash chromatography (gradient from 67% to 100% EtOAc/hex)

Sources & evidence

ORD record
ord-34cd27ce02794002b8a682db4bcb4f5e
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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