Ethyl (3S)-piperidine-3-carboxylate → HCID 50923564, compound

HRID 1948512Notes

Reaction equation

HRID 1948512 reaction equation
[O:1]1[CH2:3][CH:2]1[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[C:13]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:16]=3[C:26]([F:29])([F:28])[F:27])[O:12][N:11]=2)=[C:6]([C:30]([F:33])([F:32])[F:31])[CH:5]=1.[NH:34]1[CH2:39][CH2:38][CH2:37][C@H:36]([C:40]([O:42]CC)=[O:41])[CH2:35]1>CCO>[OH:1][CH:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[C:13]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:16]=3[C:26]([F:28])([F:27])[F:29])[O:12][N:11]=2)=[C:6]([C:30]([F:32])([F:31])[F:33])[CH:5]=1)[CH2:3][N:34]1[CH2:39][CH2:38][CH2:37][C@H:36]([C:40]([OH:42])=[O:41])[CH2:35]1

Participants

4

Reactant 2

HCID 187784Ethyl (3S)-piperidine-3-carboxylateHCID 86656397HCID 86656397, compound

Product 1

HCID 50923564HCID 50923564, compoundYield 37.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-(4-(oxiran-2-yl)-2-(trifluoromethyl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole (50 mg, 0.107 mmol) in EtOH (5 mL) was added (S)-ethyl piperidine-3-carboxylate (50.5 mg, 0.321 mmol). The reaction mixture was heated at 80° C. overnight and solvents were removed in vacuo. The mixture was treated with 6N HCl in MeCN at 50° C. for 24 h. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 24 mg of (3S)-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)-3-(trifluoromethyl)phenyl)ethyl)piperidine-3-carboxylic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 7.99-8.06 (1H, m), 7.91-7.96 (1H, m), 7.81-7.90 (1H, m), 7.59 (2H, d, J=6.59 Hz), 7.44-7.56 (3H, m), 3.69-4.04 (1H, m), 3.34-3.64 (3H, m), 3.26-3.35 (2H, m), 2.72-3.14 (2H, m), 2.00-2.22 (1H, m), 1.75-2.00 (2H, m), 1.56 (1H, t, J=12.81 Hz). MS (m+1)=597. HPLC Peak RT=3.4 minutes (Analytical Method A). Purity=92%.

Workup

  1. customsolvents were removed in vacuo
  2. additionThe mixture was treated with 6N HCl in MeCN at 50° C. for 24 h
  3. filtrationThe reaction mixture was filtered
  4. custompurified by HPLC
  5. custom25 minute
  6. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-55ede457a44b4afdb23faceae66408fb
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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