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

HRID 924330Notes

Reaction equation

HRID 924330 reaction equation
C([C@@H]1[CH2:13][CH:12]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[N:11](/C=C/C2C=CC=CC=2)[C:10]1=[O:35])(=O)C1C=CC=CC=1.[CH2:36]=O.[CH3:38][C:39]([CH3:42])([O-:41])[CH3:40].[K+].CO[CH2:46][CH2:47][O:48]C>[Cl-].[NH4+]>[C:39]([O:41][C:10]([N:11]1[C@H:12]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[CH2:13][C:46](=[CH2:36])[C:47]1=[O:48])=[O:35])([CH3:42])([CH3:40])[CH3:38]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 80711,2-DimethoxyethaneHCID 23665647Potassium tert-butoxideHCID 86673650HCID 86673650, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
20 °C

Procedure

The mixture of (R/S)-3-Benzoyl-(S)-5-biphenyl-4-ylmethyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (4a, R1=t-butoxycarbonyl, R4=phenyl) (0.45 5 g, 1 mmol), paraformaldehyde (60 mg, 2 mmol) and potassium-tert-butoxide (0.148 g, 1.3 mmol) in 5 mL dry DME is stirred for 2 hours at 20° C. Then the reaction mixture is diluted with 5 mL saturated aqueous ammonium chloride solution and stirred for 15 min, stop stirring, and remove the lower aqueous layer. the organic phase is then concentrated in vacuo. ethyl acetate 10 mL is added, filtered and the filtrate concentrated and purified by column chromatography eluting with 5:1 heptane/ethyl acetate to afford (R)-5-Biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butylester (1a, R1=t-butoxycarbonyl). Spectroscopic data as reported in WO2009/090251 (Example 23, Method 1).

Workup

  1. stirringstirred for 15 min
  2. stirringstop stirring
  3. customremove the lower aqueous layer
  4. concentrationthe organic phase is then concentrated in vacuo
  5. additionethyl acetate 10 mL is added
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated
  8. custompurified by column chromatography
  9. washeluting with 5:1 heptane/ethyl acetate

Sources & evidence

ORD record
ord-a54b063007cb45c49f4d2715096b3754
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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