Trifluoroacetic acid → HCID 57998014, compound

HRID 2425790Notes

Reaction equation

HRID 2425790 reaction equation
[C:1]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([S:16][CH3:17])[CH2:11][NH:10][C@H:9]([C:12]([O:14][CH3:15])=[O:13])[CH2:8]2)=[CH:3][CH:2]=1.C(O)(C(F)(F)F)=O.[C:31]([O:35][C:36]([NH:38][C@@H:39]([C:43]([CH3:46])([CH3:45])[CH3:44])[C:40](O)=[O:41])=[O:37])([CH3:34])([CH3:33])[CH3:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:1]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:2]=[CH:3][C:4]([C@@:7]2([S:16][CH3:17])[CH2:11][N:10]([C:40](=[O:41])[C@@H:39]([NH:38][C:36]([O:35][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:37])[C:43]([CH3:46])([CH3:45])[CH3:44])[C@H:9]([C:12]([O:14][CH3:15])=[O:13])[CH2:8]2)=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2734668(S)-2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57998009HCID 57998009, compound

Product 1

HCID 57998014HCID 57998014, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an iced slurry of (2S,4R)-methyl 4-(biphenyl-4-yl)-4-(methylthio)pyrrolidine-2-carboxylate, TFA (174 mg, 0.394 mmol), (S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (100 mg, 0.434 mmol), and HATU (225 mg, 0.591 mmol) in DCM (5 mL) was added N,N-Diisopropylethylamine (0.207 mL, 1.182 mmol). The formed colorless slurry was stirred at room temperature overnight. Diluted with DCM, quenched with 5% citric acid. The organic layer was washed with 0.1 M NaOH and brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by BIOTAGE® column, eluted with 5˜35% etOAc-hexane to yield the desired product (2S,4R)-methyl 4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(methylthio)pyrrolidine-2-carboxylate (178 mg, 0.296 mmol, 75% yield) as a white solid. 1H NMR (500 MHz, MeOD) ppm 1.12 (s, 9H), 1.46 (s, 9H), 1.86 (s, 3H), 2.60 (dd, J=12.97, 6.87 Hz, 1H), 2.90 (dd, J=12.82, 7.93 Hz, 1H), 3.74 (s, 3H), 4.11 (d, J=11.29 Hz, 1H), 4.35-4.48 (m, 2H), 4.73 (d, J=10.99 Hz, 1H), 7.36 (t, J=7.02 Hz, 1H), 7.42-7.51 (m, 3H), 7.54-7.71 (m, 5H). LC-MS (retention time: 3.34 min, method B), MS m/z 541 (M+H).

Workup

  1. customquenched with 5% citric acid
  2. washThe organic layer was washed with 0.1 M NaOH and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by BIOTAGE® column
  7. washeluted with 5˜35% etOAc-hexane

Sources & evidence

ORD record
ord-2c67fb29f9314e0b8d1f4ea5c07317ce
Source dataset
uspto-grants-2011_06
Patent number
US07964560B2

Reaction notes

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