Tetrahydrofuran → (R)-5-Biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butylester

HRID 2174843Notes

Reaction equation

HRID 2174843 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:11]/[C:10](=[CH:26]\N(C(C)C)C(C)C)/[C:9]1=[O:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[H-].C([Al+]CC(C)C)C(C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:18][CH:19]=2)[CH2:11][C:10](=[CH2:26])[C:9]1=[O:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 9357Potassium Sodium TartrateHCID 21225700DiisobutylaluminumhydrideHCID 58160400(r)-5-Biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(e)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 46193438(R)-5-Biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butylester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

(R)-5-Biphenyl-4-ylmethyl-3-[1-dimethylaminometh-(E/Z)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (7-a, R1=Boc, R6=Me, R7=Me) (7 g) is added to THF (210 ml) and the resulting mixture cooled to −78° C. Diisobutylaluminium hydride (109 ml, 103 mmol; 0.95 M in THF) is added over 1.5 h. To the mixture is then added Rochelle's Salt (430 ml; 1.2 M in water) and the mixture stirred vigorously. Ethyl acetate (400 ml) is added and the phases are separated. The organic phase is concentrated in vacuo. The resulting residue is dissolved in ethyl acetate (20 ml) and washed with brine (20 ml). Phases are separated. The organic phase is then concentrated in vacuo. Diethyl ether (50 ml) is added, filtered and the filtrate concentrated to give (R)-5-biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (4-a, R1=Boc).

Workup

  1. customthe phases are separated
  2. concentrationThe organic phase is concentrated in vacuo
  3. dissolutionThe resulting residue is dissolved in ethyl acetate (20 ml)
  4. washwashed with brine (20 ml)
  5. customPhases are separated
  6. concentrationThe organic phase is then concentrated in vacuo
  7. additionDiethyl ether (50 ml) is added
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated

Sources & evidence

ORD record
ord-b716b709f1854b4194ac87b7f4d701d0
Source dataset
uspto-grants-2015_06
Patent number
US09061973B2

Reaction notes

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