tert-Butyl 4-formylpiperidine-1-carboxylate → HCID 71255024, compound

HRID 540278Notes

Reaction equation

HRID 540278 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](OC(F)(F)F)[CH:10]=2)[N:5]=[C:4]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[S:20](=O)(=O)[CH2:19][CH2:18]2)[CH:3]=1.[CH2:30]([Li])CCC.[CH:35]([CH:37]1[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]1)=[O:36]>O1CCCC1.[Cl-].[NH4+]>[S:20]1[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[CH2:23][N:17]([C:4]2[CH:3]=[C:2]([CH:35]([OH:36])[CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:30])[CH:10]=3)[N:5]=2)[CH2:18][CH2:19]1

Participants

6

Reactant 3

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 712545694-(4-Chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxideHCID 178418339Butyllithium

Product 1

HCID 71255024HCID 71255024, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 4-(4-bromo-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine (385 mg, 1.0 mmol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1) in tetrahydrofuran (10 mL) which was cooled to −78° C., butyl lithium (0.8 mL, 1.3 mmol) was added slowly and the mixture was stirred for 5 minutes, followed by the addition of a solution of tert-butyl 4-formylpiperidine-1-carboxylate (153 mg, 1.3 mmol) in tetrahydrofuran (5 mL) slowly. After being stirred further at −78° C. for 2 hours, the reaction mixture was diluted with a saturated aqueous solution of ammonium chloride (10 mL) and extracted with dichloromethane (20 mL×2). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluting with 20-40% ethyl acetate in petroleum ether) to afford 360 mg of the desired product (yield was 70%). MS (ESI+) [(M+H)+] 520.

Workup

  1. stirringAfter being stirred further at −78° C. for 2 hours
  2. extractionextracted with dichloromethane (20 mL×2)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel (eluting with 20-40% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-951b0bf91f9e445a8341b4b79206e5cc
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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