Triethylamine → (R)-1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide

HRID 858926Notes

Reaction equation

HRID 858926 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[C:18](=[O:19])[CH2:17][C@@H:16]([C:20](O)=[O:21])[CH2:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:25]([N:27](CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.CN>CN(C)C=O>[CH3:25][NH:27][C:20]([C@@H:16]1[CH2:17][C:18](=[O:19])[N:14]([C:11]2[CH:12]=[CH:13][C:8]([O:7][CH2:6][C:5]3[CH:23]=[CH:24][C:2]([F:1])=[CH:3][CH:4]=3)=[CH:9][CH:10]=2)[CH2:15]1)=[O:21]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 6364545Methylamine hydrochlorideHCID 40802443(R)-1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

Product 1

HCID 10360007(R)-1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamideYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1.82 mmol of (R)-1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid in 37 ml of N,N-dimethylformamide was cooled to 0° C., was treated consecutively with 2.0 mmol of triethylamine, 1.82 mmol of HBTU, 2.2 mmol of methylamine hydrochloride, and 2.0 mmol of triethylamine. The ice-bath was removed, and stirring continued at RT. The reaction was stopped after 30 min, and the orange coloured solution was evaporated under reduced pressure. The residue obtained was triturated in 1 ml of ethyl acetate; the white solid product was filtered, thereafter dissolved in dichloromethane; and the solution washed three times with water. The organic phase was dried over sodium sulfate, then evaporated under reduced pressure to yield 409 mg (66% of theory) of the (R)-1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide a white solid. MS: m/e=343 (M+H)+; enantiomeric excess >99.5%.

Workup

  1. customThe ice-bath was removed
  2. customcontinued at RT
  3. customthe orange coloured solution was evaporated under reduced pressure
  4. customThe residue obtained
  5. customwas triturated in 1 ml of ethyl acetate
  6. filtrationthe white solid product was filtered
  7. dissolutiondissolved in dichloromethane
  8. washand the solution washed three times with water
  9. dry with materialThe organic phase was dried over sodium sulfate
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-2793309d4fd5487ca8ec3c3c7035d269
Source dataset
uspto-grants-2006_12
Patent number
US07148362B2

Reaction notes

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