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

HRID 1244579Notes

Reaction equation

HRID 1244579 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:17](=[O:18])[CH2:16][C@H:15]([C:19](O)=[O:20])[CH2:14]2)=[CH:9][CH:8]=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.C(Cl)Cl>[CH3:25][NH:27][C:19]([C@@H:15]1[CH2:16][C:17](=[O:18])[N:13]([C:10]2[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]3[CH:22]=[CH:23][CH:24]=[C:2]([F:1])[CH:3]=3)=[CH:8][CH:9]=2)[CH2:14]1)=[O:20]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 6364545Methylamine hydrochlorideHCID 67409315(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

Product 1

HCID 10020247(R)-1-[4-(3-Fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 0.339 g (1.03 mmol) of (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid in 21 ml of N,N-dimethylformamide, cooled to 0° C., is treated consecutively with 0.15 ml (1.13 mmol) of triethylamine, 0.390 g (1.03 mmol) of HBTU, 0.085 g (1.24 mmol) of methylamine hydrochloride, and 0.15 ml (1.13 mmol) of triethylamine. The reaction is stopped after 30 min and the orange colored solution is evaporated under reduced pressure. The residue obtained is triturated in ethyl acetate, the white solid product is filtered, thereafter dissolved in dichloromethane and the solution washed three times with water. The organic phase is dried over sodium sulfate, then evaporated under reduced pressure to yield 231 mg (66% of theory) of a white solid. MS: m/e=343 (M+H)+; [α]589=−25.48° (c=0.954, CH2Cl2).

Workup

  1. customthe orange colored solution is evaporated under reduced pressure
  2. customThe residue obtained
  3. customis triturated in ethyl acetate
  4. filtrationthe white solid product is filtered
  5. dissolutiondissolved in dichloromethane
  6. washthe solution washed three times with water
  7. dry with materialThe organic phase is dried over sodium sulfate
  8. customevaporated under reduced pressure
  9. customto yield 231 mg (66% of theory) of a white solid

Sources & evidence

ORD record
ord-44945f33c9ed426aa6d0dd98d7c1cc40
Source dataset
uspto-grants-2006_10
Patent number
US07122562B2

Reaction notes

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