Tributylphosphine → (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-phenylpyrrolidin-2-one

HRID 1696158Notes

Reaction equation

HRID 1696158 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C(P(CCCC)CCCC)CCC.[Cl:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[N:37]([C@@H:41]([CH2:51][CH2:52]O)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:43])[CH2:36][CH2:35][CH2:34]2>C1COCC1>[Cl:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[N:37]([C@H:41]1[CH2:51][CH2:52][N:44]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:42]1=[O:43])[CH2:36][CH2:35][CH2:34]2

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 59465889(S)-2-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-phenylbutanamide

Product 1

HCID 58215259(S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-phenylpyrrolidin-2-oneYield 100.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Prepared using general procedure 61: To a yellow solution of di-tert-butyl azo-dicarboxylate (2.23 g, 9.7 mmol) in THF (25 mL) at 0° C. under N2 was slowly added tributylphosphine (2.4 mL, 9.7 mmol), The resulting colorless solution of the Mitsunobu reagent was stirred at RT for 10 min, and then added to a solution of (S)-2-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-phenylbutanamide (2.56 g, 7.4 mmol) in THF (25 mL) at 0° C. under N2. The reaction mixture was stirred for 10 min. at this temperature, and quenched by addition of a saturated aqueous NaHCO3 solution. EtOAc was added, the phases were separated, and the aqueous layer was extracted with EtOAc (2×). The combined organic extracts were dried over MgSO4 and concentrated. Purification via silica gel chromatography using 20-40 EtOAc in hexane gave (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-phenylpyrrolidin-2-one as a white solid (2.43 g, 100%). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=327.5; tR=1.50 min.

Workup

  1. customPrepared
  2. customat 0° C.
  3. customquenched by addition of a saturated aqueous NaHCO3 solution
  4. additionEtOAc was added
  5. customthe phases were separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. concentrationconcentrated
  9. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-846fb594e12440aaa3309f0c1181ad69
Source dataset
uspto-grants-2012_04
Patent number
US08163720B2

Reaction notes

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