4-(N-Boc-amino)piperidine → {1-[2-(6-Methoxy-quinolin-3-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 1019939Notes

Reaction equation

HRID 1019939 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[N:23]=[CH:22][C:21]([S:27][CH2:28][CH:29]=O)=[CH:20]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:29][CH2:28][S:27][C:21]2[CH:22]=[N:23][C:24]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:16][CH3:15])=[CH:26][CH:25]=3)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7238334-(N-Boc-amino)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 86662005(6-Methoxy-quinolin-3-ylsulfanyl)-acetaldehyde

Product 1

HCID 66747427{1-[2-(6-Methoxy-quinolin-3-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl esterYield 10.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Piperidin-4-yl-carbamic acid tert-butyl ester (3.4 g, 17.15 mmol, 1.0 eq) is added at room temperature to a stirred solution of (6-methoxy-quinolin-3-ylsulfanyl)-acetaldehyde (4.0 g, 17.15 mmol, 1.0 eq) in 1,2-dichloroethane (200 mL), followed by sodium triacetoxyborohydride (2.06 g, 34.3 mmol, 2.0 eq). After 1 hour stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×50 mL) and a saturated sodium hydrogen carbonate aqueous solution (50 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: dichloromethane:methanol, 20:1 to 10:1, v/v) to give a yellow solid that is further recrystallized with ethyl acetate:hexane (1:6, v/v) to afford {1-[2-(6-methoxy-quinolin-3-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester as a yellow oil (724 mg, 10% yield).

Workup

  1. extractionthe reaction mixture is extracted with dichloromethane (3×50 mL)
  2. dry with materialThe combined organic layers are dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a crude product that
  6. customis purified by column chromatography (silica gel, eluent
  7. customdichloromethane:methanol, 20:1 to 10:1, v/v) to give a yellow solid
  8. customthat is further recrystallized with ethyl acetate:hexane (1:6, v/v)

Sources & evidence

ORD record
ord-b5b320835f834e2b9fd67652f1057402
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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