Thiazole → HCID 70982631, compound

HRID 2272661Notes

Reaction equation

HRID 2272661 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.[C:11]([C@H:14]1[CH2:18][N:17]([C@H:19]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH3:20])[C:16](=[O:29])[CH2:15]1)(=[O:13])[CH3:12]>C1COCC1>[OH:13][C@@:11]([C@H:14]1[CH2:18][N:17]([C@H:19]([C:21]2[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=2)[CH3:20])[C:16](=[O:29])[CH2:15]1)([C:2]1[S:1][CH:5]=[CH:4][N:3]=1)[CH3:12].[OH:13][C@:11]([C@H:14]1[CH2:18][N:17]([C@H:19]([C:21]2[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=2)[CH3:20])[C:16](=[O:29])[CH2:15]1)([C:2]1[S:1][CH:5]=[CH:4][N:3]=1)[CH3:12]

Participants

6

Reactant 3

HCID 9256ThiazoleHCID 58071853(R)-4-Acetyl-1-((S)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-oneHCID 178418339Butyllithium

Product 2

HCID 70982631HCID 70982631, compoundHCID 86715341HCID 86715341, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of thiazole (3.13 mL, 44 mmol) in THF (50 mL) at −78° C. was added nBuLi at such a rate that the internal temperature did not exceed −65° C. The reaction mixture was stirred for 15 minutes, and then a solution of (4R)-4-acetyl-1-[(1S)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-one (10 g, 38.3 mmol) in THF (50 mL) was added via canula at such a rate that the internal temperature did not exceed −65° C. The mixture was stirred for 1 hour, quenched with saturated aqueous ammonium chloride (50 mL), and warmed to room temperature. EtOAc (50 mL) and water (50 mL) were added. The layers were separated, and the aqueous layer was extracted a second time with EtOAc (50 mL). The organic layers were combined, dried over MgSO4, filtered, absorbed on silica, and purified by silica gel chromatography to afford (4R)-4-[(1S)-1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]-1-[(1S)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-one and (4R)-4-[(1R)-1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]-1-[(1S)-1(4-methoxyphenyl)ethyl]pyrrolidin-2-one.

Workup

  1. customdid not exceed −65° C
  2. customdid not exceed −65° C
  3. stirringThe mixture was stirred for 1 hour
  4. customquenched with saturated aqueous ammonium chloride (50 mL)
  5. additionEtOAc (50 mL) and water (50 mL) were added
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted a second time with EtOAc (50 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customabsorbed on silica
  11. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-e618e9b6b0db4954be0b29a95c430270
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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