Chloroform → tert-Butyl {1-[2-(7-fluoro-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 656859Notes

Reaction equation

HRID 656859 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH:13]=O)=[CH:4][CH:3]=1.[NH:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17]1.C(Cl)(Cl)Cl.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH2:13][N:16]2[CH2:17][CH2:18][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:20][CH2:21]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 7238334-(N-Boc-amino)piperidine3×HCID 5049666Sodium triacetoxyborohydride3×HCID 86635311(7-Fluoro-2-oxo-1(2H)-quinolinyl)acetaldehyde

Product 1

HCID 86635312tert-Butyl {1-[2-(7-fluoro-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateYield 117.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (7-fluoro-2-oxo-1(2H)-quinolinyl)acetaldehyde (594 mg; 2.89 mmol) and 1,1-dimethylethyl 4-piperidinylcarbamate (578 mg; 2.89 mmol) in a 1:1 mixture of chloroform and methanol (20 ml:20 ml) was stirred at rt under argon for 1 h. The mixture was then treated with NaBH(OAc)3 (1.83 g; 8.67 mmol) and stirred at rt for a 1 h. More 1,1-dimethylethyl 4-piperidinylcarbamate (297 mg; 1.45 mmol) was added and the reaction was stirred under the same conditions for a further 0.5 h. This was then again treated with NaBH(OAc)3 (915 mg; 4.34 mmol) and stirred at rt for a further 0.75 h. More 1,1-dimethylethyl 4-piperidinylcarbamate (118 mg; 0.578 mmol) was then added, the reaction was stirred at rt for a further 10 mins, followed by addition of NaBH(OAc)3 (366 mg; 1.73 mmol), the reaction was stirred for a further 25 mins. The solvents were removed and the crude residue purified by chromatography on silica gel using a 010% MeOH/DCM gradient to provide the impure desired compound (1.32 g, 117%)

Workup

  1. stirringstirred at rt for a 1 h
  2. stirringthe reaction was stirred under the same conditions for a further 0.5 h
  3. stirringstirred at rt for a further 0.75 h
  4. stirringthe reaction was stirred at rt for a further 10 mins
  5. stirringthe reaction was stirred for a further 25 mins
  6. customThe solvents were removed
  7. customthe crude residue purified by chromatography on silica gel using a 010% MeOH/DCM gradient

Sources & evidence

ORD record
ord-49cfae897526470ba42bd2335865a654
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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