Trifluoroacetic acid → HCID 66815235, compound

HRID 227157Notes

Reaction equation

HRID 227157 reaction equation
C(OC(=O)[NH:7][CH:8]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39](=[O:61])[N:40]([CH2:51][CH2:52][O:53][Si](C(C)(C)C)(C)C)[CH2:41][CH2:42][O:43][Si](C)(C)C(C)(C)C)=[CH:33][CH:32]=1)[C:9](=[O:30])[NH:10][CH:11]([C:20]1[NH:24][C:23]2[CH:25]=[C:26]([I:29])[CH:27]=[CH:28][C:22]=2[N:21]=1)[CH:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][C@H:8]([C:31]1[CH:32]=[CH:33][C:34]([O:37][CH2:38][C:39](=[O:61])[N:40]([CH2:51][CH2:52][OH:53])[CH2:41][CH2:42][OH:43])=[CH:35][CH:36]=1)[C:9]([NH:10][C@H:11]([C:20]1[NH:24][C:23]2[CH:25]=[C:26]([I:29])[CH:27]=[CH:28][C:22]=2[N:21]=1)[C@H:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])=[O:30]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86627922HCID 86627922, compound

Product 1

HCID 66815235HCID 66815235, compoundYield 93.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

{[4-({Bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamoyl}-methoxy)-phenyl]-[1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propylcarbamoyl]-methyl}-carbamic acid tert-butyl ester (270 mg, 0.27 mmol) was dissolved in dry dichloromethane (6 mL) and cooled in an ice bath. To the stirred solution was added triflouroacetic acid (3.12 mL, 40.5 mmol). The reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was concentrated in vacuo, dissolved in dichloromethane (1 mL) and the crude trifluoroacetate salt precipitated with ether (5 mL) and pentane (10 mL). The precipitate was triturated then filtered. The solid was taken into dichloromethane (50 mL) and tetrahydrofuran added to form a clear solution. The solution was washed with saturated aqueous sodium hydrogen carbonate (2×50 mL), the layers separated and the aqueous layer extracted with dichloromethane (4×50 mL). The combined organic extracts were dried over sodium sulfate filtered and concentrated in vacuo. The resulting solid was triturated with a mixture of ether (1 mL) and pentane (5 mL), filtered and dried to give (R)-2-amino-2-(4-{[bis-(2-hydroxy-ethyl)-carbamoyl]-methoxy}-phenyl)-N-[(1S,2S)-1-(6-iodo-1H-benzoimidazol-2-yl)-2-phenyl-propyl]-acetamide (170 mg, 93.8%).

Workup

  1. temperaturecooled in an ice bath
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutiondissolved in dichloromethane (1 mL)
  4. customthe crude trifluoroacetate salt precipitated with ether (5 mL) and pentane (10 mL)
  5. customThe precipitate was triturated
  6. filtrationthen filtered
  7. additionadded
  8. customto form a clear solution
  9. washThe solution was washed with saturated aqueous sodium hydrogen carbonate (2×50 mL)
  10. customthe layers separated
  11. extractionthe aqueous layer extracted with dichloromethane (4×50 mL)
  12. dry with materialThe combined organic extracts were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe resulting solid was triturated with a mixture of ether (1 mL) and pentane (5 mL)
  16. filtrationfiltered
  17. customdried

Sources & evidence

ORD record
ord-23e2e167e70a44519e98a8444060eaa5
Source dataset
uspto-grants-2009_07
Patent number
US07557221B2

Reaction notes

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