Trifluoroacetic acid → HCID 178440996, compound

HRID 1471029Notes

Reaction equation

HRID 1471029 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[NH:17][C:16]2[CH:18]=[CH:19][C:20]([CH:22]3[N:26]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:29][CH:28]=4)[CH:25]([C:37]4[CH:42]=[CH:41][C:40]([NH:43][C:44]([C@@H:46]5[CH2:50][CH2:49][CH2:48][N:47]5C(OC(C)(C)C)=O)=[O:45])=[CH:39][CH:38]=4)[CH2:24][CH2:23]3)=[CH:21][C:15]=2[N:14]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:33]([C:30]1[CH:31]=[CH:32][C:27]([N:26]2[C@@H:22]([C:20]3[CH:19]=[CH:18][C:16]4[NH:17][C:13]([C@@H:9]5[CH2:10][CH2:11][CH2:12][NH:8]5)=[N:14][C:15]=4[CH:21]=3)[CH2:23][CH2:24][C@@H:25]2[C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:44]([C@@H:46]3[CH2:50][CH2:49][CH2:48][NH:47]3)=[O:45])=[CH:41][CH:42]=2)=[CH:28][CH:29]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178451941HCID 178451941, compound

Product 1

HCID 178440996HCID 178440996, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Example 179H (0.302 g, 0.389 mmol) in CH2Cl2 (3 mL) was added TFA (2.5 mL), and the resulting mixture was stirred at rt for 1.5 h. The mixture was concentrated in vacuo, and the crude product was purified by reversed-phase HPLC (C18) using a solvent gradient of 10-100% acetonitrile in H2O (0.1% TFA). The trans-pyrrolidine isomer eluted before the cis-pyrrolidine isomer. Fractions containing the trans-isomer were concentrated in vacuo, and the residue was partitioned between CH2Cl2 and saturated aq. NaHCO3. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (83 mg, 37%).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe crude product was purified by reversed-phase HPLC (C18)
  3. washThe trans-pyrrolidine isomer eluted before the cis-pyrrolidine isomer
  4. additionFractions containing the trans-isomer
  5. concentrationwere concentrated in vacuo
  6. customthe residue was partitioned between CH2Cl2 and saturated aq. NaHCO3
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ef1e0fc482cc40529f4e2331b48bb019
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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