1-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid → HCID 15952444, compound

HRID 1642212Notes

Reaction equation

HRID 1642212 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN(C)CCCN=C=NCC.[F:29][C:30]([F:47])([F:46])[O:31][C:32]1[CH:45]=[CH:44][C:35]([O:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[NH2:43])=[CH:34][CH:33]=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:16])[NH:43][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[O:36][C:35]2[CH:44]=[CH:45][C:32]([O:31][C:30]([F:29])([F:46])[F:47])=[CH:33][CH:34]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59820835HCID 59820835, compound

Product 1

HCID 15952444HCID 15952444, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (HVB01062, 1.19 g, 5.2 mmol) was dissolved in anhydrous DCM (40 ml), and stirred under nitrogen. To this was added N N-4-dimethylaminopyridine (cat.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.0 g, 4.2 mmol) and TEA (0.84 ml). Stirred for 30 min. 2-(4-Trifluoromethoxy-phenoxy)-phenylamine (HVB01053, 1.4 g, 5.2 mmol) was added and stirred under nitrogen for 20 h. Diluted with DCM, washed with HCl (1M, 20 ml), Sodium hydrogen carbonate (sat. 20 ml), and brine (20 ml). Organic layers combined and dried over anhydrous magnesium sulphate, and evaporated in-vacuo. The crude mixture was purified using flash chromatography (DCM/hexane, 0 to 100%), to afford a yellow solid, 1.59 g, 57%. m.p. 45-48° C., Rf. 0.65 (DCM), 1HNMR: (CDCl3, 270 MHz) δ 1.44 (9H, s, CH3), 1.67 (2H, td, J=13.4, 4.4 Hz, CH2), 1.80 (2H, dd, J=1.8 Hz, CH2), 2.36 (1H, m, CH), 2.74 (2H, t, J=11.9 Hz, CH2N), 4.12 (2H, d, J=11.6 Hz, CH2N), 6.85 (1H, dd, J=6.7, 1.5 Hz, Ar HD), 7.03 (2H, d, Ar HF), 7.04 (1H, m, Ar HB), 7.13 (1H, td, J=1.5, 6.4 Hz, Ar HC), 7.20 (2H, d, J=1.5, 6.4 Hz Ar HF), 7.64 (1H, s, NH), 8.40 (1H, d, J=8.2 Hz, Ar HA.

Workup

  1. stirringStirred for 30 min
  2. stirringstirred under nitrogen for 20 h
  3. washwashed with HCl (1M, 20 ml), Sodium hydrogen carbonate (sat. 20 ml), and brine (20 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customevaporated in-vacuo
  6. customThe crude mixture was purified
  7. customto afford a yellow solid, 1.59 g, 57%

Sources & evidence

ORD record
ord-d42755b20f754f2ea2c075d31a82610c
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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