Trifluoroacetic acid methylene chloride → HCID 57546240, compound

HRID 913836Notes

Reaction equation

HRID 913836 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[C:7]([CH:16]([O:18][CH2:19][C:20]3([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)[CH3:17])[CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[NH:5][N:4]=1)#[N:2].FC(F)(F)C(O)=O.C(Cl)Cl>>[C:33]1([C:20]2([CH2:19][O:18][CH:16]([C:7]3[CH:8]=[C:9]([C:12]([F:13])([F:14])[F:15])[CH:10]=[C:11]4[C:6]=3[NH:5][N:4]=[C:3]4[C:1]#[N:2])[CH3:17])[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 57546017HCID 57546017, compound

Product 1

HCID 57546240HCID 57546240, compound

Procedure

(±)-tert-Butyl 4-((1-(3-cyano-5-(trifluoromethyl)-1H-indazol-7-yl)ethoxy)methyl)-4-phenylpiperidine-1-carboxylate (40 mg, 0.08 mmol) was treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. The solvent was evaporated to afford 25 mg (77%) as a clear oil. 1H-NMR (CDCl3, 500 MHz) δ 7.89 (s, 1H), 7.54 (d, J=1.8 Hz, 1H), 7.37-7.40 (m, 2H), 7.30-7.32 (m, 3H), 7.69 (m, 1H), 4.49 (q, J=6.7 Hz, 1H), 3.40 (q, J=9.2 Hz, 1H), 3.29 (d, J=9.2 Hz, 1H), 2.87-2.93 (m, 2H), 2.67-2.77 (m, 2H), 2.07-2.26 (m, 2H), 1.78-1.93 (m, 2H), 1.41 (m, 3H); 13C-NMR (126 MHz, CDCl3) δ ppm 143.2, 138.4, 129.4, 129.1, 127.2, 127.0, 126.0 (q, J=32.6 Hz), 124.7, 124.1 (q, J=273 Hz), 121.0, 120.3, 116.6, 77.3, 50.6, 42.4, 41.7, 33.1, 22.3. Mass spec.: 429.13 (MH)+.

Workup

  1. customThe solvent was removed in vacuo
  2. washAfter washing the column with several volumes of methanol
  3. washthe product was eluted
  4. washby washing the column with 2 M ammonia in methanol
  5. customThe solvent was evaporated
  6. customto afford 25 mg (77%) as a clear oil

Sources & evidence

ORD record
ord-b363648935474b50b9deba9aeb116e41
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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