Trifluoroacetic acid → HCID 69292167, compound

HRID 1391981Notes

Reaction equation

HRID 1391981 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([CH2:19][NH:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[C@@H:14]([OH:18])[C:15]#[C:16][CH3:17])[C:9]1=[O:31])(C)(C)C.C(O)(C(F)(F)F)=O.C(N(CC)C(C)C)(C)C.[C:49]([NH:56][C:57]1[CH:65]=[CH:64][C:63]([C:66]([F:69])([F:68])[F:67])=[CH:62][C:58]=1[C:59]([OH:61])=O)([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:52]([O:51][C:49](=[O:50])[NH:56][C:57]1[CH:65]=[CH:64][C:63]([C:66]([F:69])([F:68])[F:67])=[CH:62][C:58]=1[C:59](=[O:61])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([CH2:19][NH:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[C@@H:14]([OH:18])[C:15]#[C:16][CH3:17])[C:9]1=[O:31])([CH3:53])([CH3:55])[CH3:54]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 150338862-((tert-Butoxycarbonyl)amino)-5-(trifluoromethyl)benzoic acidHCID 67271775HCID 67271775, compound

Product 1

HCID 69292167HCID 69292167, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of {(3S)-1-[(1S,2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-2-oxo-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (0.097 mg, 0.22 mmol, see procedure 1b above) was dissolved in CH2Cl2 (4 mL) and treated with TFA (2 mL). The solution was stirred for 3 h and then concentrated in vacuo. The residue was dissolved in CH2Cl2 and concentrated in vacuo; this procedure was repeated. The product amine was dissolved in 1:1 DMF/CH2Cl2 (4 mL). The resultant solution was charged sequentially with N, N-diisopropylethylamine (0.16 mL, 0.88 mmol), N-Boc-2-amino-5-(trifluoromethyl)-benzoic acid (S. Takagishi, et al., Synlett 1992, 360; 73 mg, 0.24 mmol), and HATU (97 mg, 0.26 mmol). The reaction was stirred for 12 h and partitioned between EtOAc and sat. NH4Cl. The organic phase was washed with sat. NaHCO3 and brine, and then dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography afforded (2-{(3S)-1-[(1S,2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-2-oxo-pyrrolidin-3-ylcarbamoyl}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester(87 mg, 64% yield). MS found: (M+Na)+=655.5.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2
  3. concentrationconcentrated in vacuo
  4. dissolutionThe product amine was dissolved in 1:1 DMF/CH2Cl2 (4 mL)
  5. stirringThe reaction was stirred for 12 h
  6. custompartitioned between EtOAc and sat. NH4Cl
  7. washThe organic phase was washed with sat. NaHCO3 and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by flash chromatography

Sources & evidence

ORD record
ord-d0433cd2282c43969512ab241638bf64
Source dataset
uspto-grants-2008_03
Patent number
US07338975B2

Reaction notes

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