Trifluoroacetic acid → (1-acetyl-3-{4-[3-(pyridin-2-ylamino)propoxy]benzyl}piperidin-3-yl)acetic Acid

HRID 1860649Notes

Reaction equation

HRID 1860649 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH2:7][C:6]([CH2:28][C:29]([O:31]CC)=[O:30])([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[CH:13][CH:12]=2)[CH2:5]1)(=[O:3])[CH3:2].FC(F)(F)C(O)=O>CO.[OH-].[Na+]>[C:1]([N:4]1[CH2:9][CH2:8][CH2:7][C:6]([CH2:28][C:29]([OH:31])=[O:30])([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[CH:13][CH:12]=2)[CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 12018737Ethyl (1-acetyl-3-{4-[3-(pyridin-2-ylamino)propoxy]benzyl}piperidin-3-yl)acetate

Product 1

HCID 10295998(1-acetyl-3-{4-[3-(pyridin-2-ylamino)propoxy]benzyl}piperidin-3-yl)acetic Acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

The product from STEP 10 (125 mg) was dissolved in 10 ml methanol and 10 ml 1N sodium hydroxide solution. The reaction was stirred at room temperature for 18 h, then acidified with trifluoroacetic acid (0.77 ml), and concentrated. The residue was purified on reverse phase HPLC using acetonitrile gradient 10-50% in 30 min to yield 90.7 mg. MS: (M+1)=426.2. 1H NMR (CD3CN) δ1.39-1.76 (cmplx bnd, 4H); 2.15, 2.07 (s, 3H); 2.12 (p, 2H); 2.14, 2.10 (d, 1IH); 2.17, 2.28 (d, 1H); 2.68, 2.75 (d, 1H); 2.73, 2.77 (d, 1H); 3.23, 3.14 (ddd, 1H); 3.11, 3.28 (d, 1H); 3.54 (t, 2H); 3.76, 3.68, (d, 1H); 3.61, 3.86 (dd, 1H); 4.08 (t, 2H); 6.82 (t, 1H); 6.85, 6.87 (d, 2H); 7.01 (d, 1H); 7.17, 7.13 (d, 2H); 7.73 (d, 1H); 7.86 (t, 1H). Note: many signals are doubled due to restricted rotation about amide bond. Two chemical shifts are listed for protons which have different shifts in the rotamers, with chemical shift of major rotamer listed first. Anal Calcd. for C24H31N3O4 plus 2.2 CF3COOH: C, 49.77; H, 5.03; N, 6.13. Found: C, 49.47; H, 5.11; N, 6.49.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified on reverse phase
  3. customin 30 min
  4. customto yield 90.7 mg

Sources & evidence

ORD record
ord-9470bb31e2274bf7831fb658fe405627
Source dataset
uspto-grants-2003_03
Patent number
US06531494B1

Reaction notes

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