4-(N-Boc-amino)piperidine → {1-[2-(7-Methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 1422749Notes

Reaction equation

HRID 1422749 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:26]=[C:25]2[C:20]([N:21]=[CH:22][C:23]([S:27][CH2:28][CH:29]=O)=[N:24]2)=[CH:19][CH:18]=1.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:23]2[CH:22]=[N:21][C:20]3[C:25](=[CH:26][C:17]([O:16][CH3:15])=[CH:18][CH:19]=3)[N:24]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7238334-(N-Boc-amino)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 86662002(7-Methoxy-quinoxalin-2-ylsulfanyl)-acetaldehyde

Product 1

HCID 66746671{1-[2-(7-Methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl esterYield 66.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Piperidin-4-yl-carbamic acid tert-butyl ester (2.82 g, 14.09 mmol, 1.5 eq) is added at room temperature to a stirred solution of (7-methoxy-quinoxalin-2-ylsulfanyl)-acetaldehyde (2.2 g, 9.39 mmol, 1.0 eq) in 1,2-dichloroethane (80 mL), followed by sodium triacetoxyborohydride (3.98 g, 18.78 mmol, 2.0 eq). After 15 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×60 mL) and a saturated sodium hydrogen carbonate aqueous solution (60 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: ethyl acetate:hexane, 1:1, v/v) to give a yellow solid that is further recrystallized with ethyl acetate:hexane (1:6, v/v) to afford {1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester as light yellow needles (2.6 g, 66% yield).

Workup

  1. extractionthe reaction mixture is extracted with dichloromethane (3×60 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. customethyl acetate:hexane, 1:1, 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-65fc1d53aa4546a188a2a61ba243ae45
Source dataset
uspto-grants-2015_01
Patent number
US08927542B2

Reaction notes

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