Nitrogen → HCID 57918267, compound

HRID 2266234Notes

Reaction equation

HRID 2266234 reaction equation
N#N.Br[C:4]1[C:12]2[O:11][C:10]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:9][C:8]=2[CH:7]=[CH:6][CH:5]=1.[Li]CCCC.CON(C)[C:25]([C@@H:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]1)=[O:26]>C1COCC1>[C:13]([C:10]1[O:11][C:12]2[C:4]([C:25]([C@@H:27]3[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]3)=[O:26])=[CH:5][CH:6]=[CH:7][C:8]=2[CH:9]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 947NitrogenHCID 30025965(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylateHCID 59598461HCID 59598461, compoundHCID 178418339Butyllithium

Product 1

HCID 57918267HCID 57918267, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under protection of N2, a solution of 7-bromo-2-tert-butyl-benzofuran (0.5 g, 1.98 mmol) in anhydrous THF (5 mL) was cooled to −78° C. and 2.5 M n-BuLi solution in hexanes (0.87 mL, 2.18 mmol) was added dropwise slowly. The reaction mixture was stirred at −78° C. for 1 h and a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (0.65 g, 2.38 mmol) in anhydrous THF (5 mL) was added dropwise slowly. The reaction mixture was warmed to rt and stirred overnight. The mixture was quenched with satd aq NH4Cl (20 mL) and extracted with EtOAc (3×30 mL). The combined organic extracts were dried over Na2SO4. Solvent removal and flash column chromatography afforded (R)-tert-butyl 3-(2-tert-butylbenzofuran-7-carbonyl)piperidine-1-carboxylate (0.41 g, 54%). 1H NMR (CDCl3): 7.83 (d, 1H), 7.19 (d, 1H), 7.26 (t, 1H), 6.440 (s, 1H), 4.1 (d, 1H), 3.75 (s, 1H), 2.83 (t, 1H), 2.27 (d, 1H), 1.82 (d, 1H), 1.590 (m, 4H), 1.426 (s, 9H), 1.406 (s, 9H)

Workup

  1. temperatureThe reaction mixture was warmed to rt
  2. stirringstirred overnight
  3. customThe mixture was quenched with satd aq NH4Cl (20 mL)
  4. extractionextracted with EtOAc (3×30 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. customSolvent removal and flash column chromatography

Sources & evidence

ORD record
ord-63e9329acf804d6e875dc8211a043487
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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