Trifluoroacetic acid → N-((1R,2S)-1-(4-(5-(aminomethyl)thiophen-2-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)-2,2-dichloroacetamide

HRID 525504Notes

Reaction equation

HRID 525504 reaction equation
[Cl:1][CH:2]([Cl:31])[C:3]([NH:5][C@H:6]([CH2:29][F:30])[C@@H:7]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:19][C:18]([CH2:20][NH:21]C(=O)OC(C)(C)C)=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[OH:8])=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:21][CH2:20][C:18]1[S:19][C:15]([C:12]2[CH:11]=[CH:10][C:9]([C@@H:7]([OH:8])[C@H:6]([NH:5][C:3](=[O:4])[CH:2]([Cl:31])[Cl:1])[CH2:29][F:30])=[CH:14][CH:13]=2)=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86695382tert-butyl ((5-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiophen-2-yl)methyl)carbamate

Product 1

HCID 86695384N-((1R,2S)-1-(4-(5-(aminomethyl)thiophen-2-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)-2,2-dichloroacetamideYield 60.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((5-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiophen-2-yl)methyl)carbamate (140 mg, 0.238 mmol) in CH2Cl2 (10 mL) is added trifluoroacetic acid (1.0 mL) and the reaction mixture stirred at room temperature for 2 hours. The solvent is removed under reduced pressure and the residue washed with diethyl ether, then dissolved in 10% methanol in CH2Cl2 and evaporated to dryness. Washed with n-pentane and dried under vacuum to give the title compound (56 mg): 1HNMR (400 MHz, DMSO-d6) δ: 4.19-4.21 (m, 1H), 4.24-4.26 (m, 2H), 4.29-4.31 (m, 0.5H), 4.39-4.43 (m, 0.5H), 4.55-4.59 (m, 0.5H), 4.67-4.70 (m, 0.5H), 4.87 (bs, 1H), 5.90 (bs, 1H) 6.50 (s, 1H), 7.20 (d, J=3.64 Hz, 1H), 7.39 (d, J=8.24 Hz, 2H), 7.43 (d, J=3.68 Hz, 1H), 7.57 (d, J=8.16 Hz, 2H), 8.20 (bs, 3H), 8.59-8.63 (m, 1H). m/z (Cl) 388 [M−H].

Workup

  1. customThe solvent is removed under reduced pressure
  2. washthe residue washed with diethyl ether
  3. dissolutiondissolved in 10% methanol in CH2Cl2
  4. customevaporated to dryness
  5. washWashed with n-pentane
  6. customdried under vacuum

Sources & evidence

ORD record
ord-e4675e88da1d43978d776942ea5c85cc
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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