Trifluoroacetic acid → HCID 51354738, compound

HRID 1874632Notes

Reaction equation

HRID 1874632 reaction equation
[CH3:1][C@@H:2]([CH2:41][CH3:42])[C@H:3]([NH:33]C(=O)OC(C)(C)C)[C:4]([NH:6][CH2:7][C@@H:8]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH:28]([CH3:32])[CH2:29][CH2:30][CH3:31])=[CH:22][CH:21]=1)[NH:9][C:10](=[O:19])[C@H:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:12])=[O:5].C(O)(C(F)(F)F)=O>ClCCl>[NH2:33][C@@H:3]([C@@H:2]([CH3:1])[CH2:41][CH3:42])[C:4]([NH:6][CH2:7][C@@H:8]([C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH:28]([CH3:32])[CH2:29][CH2:30][CH3:31])=[CH:24][CH:25]=1)[NH:9][C:10](=[O:19])[C@H:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:12])=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86658400HCID 86658400, compound

Product 1

HCID 51354738HCID 51354738, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of t-butyl (2S,3S)-3-methyl-1-((2R)-2-(4-(2-methylpentyloxy)phenyl)-2-((S)-2-phenylpropanamido)ethylamino)-1-oxopentan-2-ylcarbamate (80 mg, 0.138 mmol) in dichloromethane (2 mL) was added TFA (1 mL, 12.98 mmol). The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated and the residue was transferred to a separatory funnel containing saturated aqueous K2CO3 solution. The aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. 1H NMR indicated that the product was still a TFA salt. The product was dissolved in methanol and passed through a cation exchange resin (washed with methanol and water to remove the acid followed by 2M ammonia in methanol to elute the product) to afford (2S,3S)-2-amino-3-methyl-N-((2R)-2-(4-(2-methylpentyloxy)phenyl)-2-((S)-2-phenylpropanamido)ethyl)pentanamide (51 mg, 77% yield) as a colorless solid as the free base: 1H NMR (400 MHz, CDCl3) δ 7.70 (t, J=6.2 Hz, 1H), 7.26-7.33 (m, 2H), 7.19-7.26 (m, 3H), 6.93 (d, J=6.5 Hz, 1H), 6.87 (d, 2H), 6.70 (d, J=8.6 Hz, 2H), 4.89 (ddd, J=9.5, 6.4, 3.5 Hz, 1H), 3.72 (dd, J=8.8, 5.8 Hz, 1H), 3.62 (dd, J=8.8, 6.8 Hz, 1H), 3.45-3.57 (m, 2H), 3.35 (ddd, J=14.0, 5.7, 3.9 Hz, 1H), 3.23 (d, J=3.5 Hz, 1H), 1.93-2.04 (m, 1H), 1.83-1.93 (m, 1H), 1.42 (d, J=7.1 Hz, 3H), 1.23-1.54 (m, 6H), 1.01-1.21 (m, 2H), 0.96 (d, J=6.8 Hz, 3H), 0.94 (d, J=7.3 Hz, 3H), 0.90 (t, J=7.3 Hz, 3H), 0.89 (t, J=7.1 Hz, 3H); LRMS (ESI) m/e 482.5 [(M+H)+, calcd for C29H44N3O3 482.3].

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was transferred to a separatory funnel
  3. additioncontaining saturated aqueous K2CO3 solution
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe product was dissolved in methanol
  9. washwashed with methanol and water
  10. customto remove the acid
  11. washto elute the product)

Sources & evidence

ORD record
ord-9b78a293f49e443fbdbf851eba7e9069
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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