Dimethylformamide → HCID 86673845, compound

HRID 1527399Notes

Reaction equation

HRID 1527399 reaction equation
C(OC(N1C[C@:11](CN)([F:13])[CH2:10][C@H:9]1[C:16](OCC1C=CC=CC=1)=O)=O)(C)(C)C.C(Cl)(O[CH2:29][C:30]([Cl:33])(Cl)Cl)=O.[C:35]([O:39][C:40]([N:42]1[CH2:46][C@@:45]([F:57])([CH2:47][NH:48][C:49]([O:51][CH2:52][C:53]([Cl:56])([Cl:55])[Cl:54])=[O:50])[CH2:44][C@H:43]1[C:58](OCC1C=CC=CC=1)=[O:59])=[O:41])([CH3:38])([CH3:37])[CH3:36].[CH3:68]I.[H-].[Na+].C[N:73]([CH:75]=O)C>C(Cl)Cl>[C:35]([O:39][C:40]([N:42]1[CH2:46][C@@:45]([F:57])([CH2:47][N:48]([CH3:68])[C:49]([O:51][CH2:52][C:53]([Cl:54])([Cl:55])[Cl:56])=[O:50])[CH2:44][C@H:43]1[C:58](=[O:59])[NH:73][CH2:75][C:10]1[CH:9]=[CH:16][CH:29]=[C:30]([Cl:33])[C:11]=1[F:13])=[O:41])([CH3:36])([CH3:37])[CH3:38]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 870632,2,2-Trichloroethyl chloroformateHCID 68284280(2S,4S)-4-Aminomethyl-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl esterHCID 71009730(2S,4S)-4-Fluoro-4-[(2,2,2-trichloro-ethoxycarbonylamino)-methyl]-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester

Product 1

HCID 86673845HCID 86673845, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,4S)-4-aminomethyl-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (100 mg, 0.28 mmol) in CH2Cl2 (10 mL) was added Troc-Cl (0.05 mL, 0.34 mmol). The reaction mixture was stirred for 16 h at RT. The reaction mixture was quenched with water, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered, concentrated and purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1). To a solution of (2S,4S)-4-Fluoro-4-[(2,2,2-trichloro-ethoxycarbonylamino)-methyl]-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (50 mg, 0.09 mmol) and methyl iodide (0.02 mL, 0.28 mmol) in DMF (5 mL) at 0° C. was added sodium hydride (2.50 mg, 0.10 mmol) in portions. The reaction mixture was stirred 90 min at 0° C. and 16 h at RT. The reaction mixture was quenched with water, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1). MS (UPLC/MS): 541/543 [M+H]+, 586/587 [M+HCOO]−; tR (HPLC conditions f): 2.66 min.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1)
  8. stirringThe reaction mixture was stirred 90 min at 0° C. and 16 h at RT
  9. customThe reaction mixture was quenched with water
  10. extractionextracted with EtOAc
  11. washwashed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customPurification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1)
  16. custom2.66 min.

Sources & evidence

ORD record
ord-5a221a7f4ade450eb8d5b4fd14fa6e7d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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