Trifluoroacetic acid → Trifluoroacetate

HRID 1522049Notes

Reaction equation

HRID 1522049 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([CH:17]4[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]4)=[CH:16][C:9]=23)[CH:5]=[N:4][CH:3]=1.[CH:30](=O)[C:31]1[CH:36]=[CH:35][CH:34]=[N:33][CH:32]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:52][C:53]([F:58])([F:57])[C:54]([OH:56])=[O:55]>C(Cl)Cl.C(O)(=O)C.ClCCCl>[NH:20]1[CH2:19][CH2:18][CH:17]([C:15]2[NH:14][C:10]3=[N:11][CH:12]=[CH:13][C:8]([C:6]4[N:7]=[C:2]([NH:1][CH2:30][C:31]5[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=5)[CH:3]=[N:4][CH:5]=4)=[C:9]3[CH:16]=2)[CH2:22][CH2:21]1.[F:52][C:53]([F:58])([F:57])[C:54]([O-:56])=[O:55]

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 103713-PyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 90412745HCID 90412745, compound

Product 2

HCID 84468TrifluoroacetateHCID 90413661HCID 90413661, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of Example 319A (50 mg, 0.13 mmol) in a mixed solvent of 1,2-dichloroethane (1 ml) and acetic acid (0.5 ml) was added nicotinaldehyde (20 mg, 0.19 mmol). The mixture was stirred at room temperature for 2 hours and sodium triacetoxyborohydride (40 mg, 0.19 mmol) was added. The mixture was stirred overnight. The reaction mixture was partitioned between water and ethyl acetate. The organic phase was concentrated and purified by flash chromatography on silica gel using an ISCO Companion eluting with heptanes/ethyl acetate (30%) to give Boc-protected intermediate which was dissolved in CH2Cl2 (10 mL) then treated with trifluoroacetic acid (1 mL). The mixture was stirred at room temperature for 5 hours and concentrated. The residue was purified by reverse-phase HPLC on Zorbax XDB C-18 using a gradient of 5-40% acetonitrile/water (containing 0.1% trifluoroacetic acid) to afford the title compound as a trifluoroacetate salt. 1H NMR (400 MHz, DMSO-d6) δ 1.64-1.86 (m, 2H), 2.02-2.25 (m, 2H), 3.05 (dd, J=13.0, 8.4 Hz, 3H), 3.38 (d, J=12.4 Hz, 2H), 4.77 (d, J=4.5 Hz, 2H), 6.57 (s, 1H), 7.51 (d, J=5.1 Hz, 1H), 7.77 (dd, J=8.0, 5.3 Hz, 1H), 8.12 (s, 1H), 8.24 (t, J=6.3 Hz, 2H), 8.45 (s, 1H), 8.68 (d, J=5.3 Hz, 1H), 8.82 (s, 1H). MS (ESI+) m/z 386 (M+H)+.

Workup

  1. stirringThe mixture was stirred overnight
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. concentrationThe organic phase was concentrated
  4. custompurified by flash chromatography on silica gel using an ISCO Companion
  5. washeluting with heptanes/ethyl acetate (30%)
  6. customto give Boc-protected intermediate which
  7. stirringThe mixture was stirred at room temperature for 5 hours
  8. concentrationconcentrated
  9. customThe residue was purified by reverse-phase HPLC on Zorbax XDB C-18

Sources & evidence

ORD record
ord-bfa43f3387514adea45b44ddf8cf50e6
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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