4-(N-Boc-amino)piperidine → tert-Butyl {1-[2-(5,7-difluoro-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 656937Notes

Reaction equation

HRID 656937 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:16])[N:7]2[CH2:13][CH:14]=O.[NH:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH2:18]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)(Cl)Cl.CO>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:16])[N:7]2[CH2:13][CH2:14][N:17]1[CH2:18][CH2:19][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:21][CH2:22]1

Participants

6

Reactant 3

HCID 7238334-(N-Boc-amino)piperidine3×HCID 5049666Sodium triacetoxyborohydride3×HCID 86635323(5,7-Difluoro-2-oxo-1(2H)-quinolinyl)acetaldehyde

Product 1

HCID 86635322tert-Butyl {1-[2-(5,7-difluoro-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateYield 52.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

(5,7-Difluoro-2-oxo-1(2H)-quinolinyl)acetaldehyde (2.1 g; 9.4 mmol) and 1,1-dimethylethyl 4-piperidinylcarbamate (2.82 g; 14.1 mmol) were dissolved in a 1:1 mixture of chloroform and MeOH (60 ml:60 ml) and stirred at rt for 1 h. This was then treated with NaBH(OAc)3 (8.92 g; 42.3 mmol) and stirred for a further 1 h. More 1,1-dimethylethyl 4-piperidinylcarbamate (470 mg; 2.35 mmol) was added and the reaction stirred under the same conditions for 20 mins, this was then treated with NaBH(OAc)3 (1.98 g; 9.4 mmol) and stirred for 25 mins. More 1,1-dimethylethyl 4-piperidinylcarbamate (470 mg; 2.35 mmol) was then added and the reaction stirred for 20 mins. More NaBH(OAc)3 (500 mg; 2.38 mmol) was then added to the reaction and it was stirred overnight at rt. The solvents were then removed and the crude residue purified by column chromatography on silica gel using a 0-15% MeOH/DCM gradient to give the desired product (2 g; 52%).

Workup

  1. stirringstirred for a further 1 h
  2. stirringthe reaction stirred under the same conditions for 20 mins
  3. stirringstirred for 25 mins
  4. stirringthe reaction stirred for 20 mins
  5. stirringwas stirred overnight at rt
  6. customThe solvents were then removed
  7. customthe crude residue purified by column chromatography on silica gel using a 0-15% MeOH/DCM gradient

Sources & evidence

ORD record
ord-3e41ef24a08946a1a335239db6223352
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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