Trifluoroacetic acid → HCID 71554511, compound

HRID 2283171Notes

Reaction equation

HRID 2283171 reaction equation
[Cl:1][CH:2]([Cl:37])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([NH:27]C(=O)OC(C)(C)C)([CH3:26])[CH3:25])=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[O:7]C1(C)C)=[O:4].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl.C1(C)C=CC=CC=1>[NH2:27][C:24]([C:21]1[CH:22]=[CH:23][C:18]([C:15]2[CH:16]=[CH:17][C:12]([C@@H:8]([OH:7])[C@H:9]([NH:5][C:3](=[O:4])[CH:2]([Cl:37])[Cl:1])[CH2:10][F:11])=[CH:13][CH:14]=2)=[CH:19][CH:20]=1)([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 89519228HCID 89519228, compound

Product 1

HCID 71554511HCID 71554511, compoundYield 8.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Step 1 (50 mg. 0.09 mmol) in DCM (1 mL) is added TFA (0.25 mL) and stirred at room temperature for 1 hour. Reaction is diluted with toluene (5 mL) and concentrated. Crude product is dissolved in DCM (0.5 mL) and DIPEA (200 μL), adsorbed on celite and purified on silica gel column eluting from 5 to 20% MeOH/DCM. The combined fractions are concentrated to give an oil, which is basified using saturated aqueous NaHCO3 (0.5 mL), and extracted with ethyl acetate (3×2 mL). The combined extracts are dried over Na2SO4 and concentrated to give the title compound (3 mg). 1H NMR (400 MHz, CD3OD) δ 1.52 (s, 6H), 4.2-4.29 (m, 1.5H), 4.32-4.38 (m, 0.5H) 4.4-4.51 m, 1.5H), 4.55-4.61 (m, 0.5H), 4.89 (d, 1H, J=4.0 Hz) 6.19 (s, 1H), 7.38 (d, 2H, J=8.0 Hz), 7.45-7.50 (m, 3H), 7.51-7.56 (m, 3H). m/z (Cl) 396 [M-OH].

Workup

  1. customReaction
  2. concentrationconcentrated
  3. dissolutionCrude product is dissolved in DCM (0.5 mL)
  4. custompurified on silica gel column
  5. washeluting from 5 to 20% MeOH/DCM
  6. concentrationThe combined fractions are concentrated
  7. customto give an oil, which
  8. extractionextracted with ethyl acetate (3×2 mL)
  9. dry with materialThe combined extracts are dried over Na2SO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b047fb3a8e0144bdbb4637a28a1e8cc0
Source dataset
uspto-grants-2015_09
Patent number
US09145355B2

Reaction notes

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