Ammonium Chloride → HCID 90024521, compound

HRID 1057050Notes

Reaction equation

HRID 1057050 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:29][C:30]1[CH:35]=[C:34](I)[CH:33]=[CH:32][N:31]=1.[Cl-].[NH4+]>O1CCCC1.O>[Cl:29][C:30]1[CH:35]=[C:34]([C:6]2([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:8][CH2:7]2)[CH:33]=[CH:32][N:31]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 15165112-Chloro-4-iodopyridineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

Product 1

HCID 90024521HCID 90024521, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of piperidine-1,4-dicarboxylic acid 1-tert-butylester 4-ethyl ester (200 g, 0.78 mol, 1 equiv.) in dry tetrahydrofuran (350 mL) was added a 1M solution of sodium bis(trimethylsilyl)amide (1010 mL, 1.01 mol, 1.3 equiv.) drop-wise at 0° C. under nitrogen atmosphere. The reaction mixture was stirred for 1.5 h at 0° C. and added to a solution of 2-chloro-4-iodopyridine (199.2 g, 0.83 mol) in dry tetrahydrofuran (350 mL) at 0° C. under nitrogen atmosphere. The reaction mixture was kept at 0° C. for 3 hours, and was monitored by TLC (ethyl acetate/petroleum ether; 1/5). A solution of ammonium chloride (34.8 g) in water (260 mL) was added cautiously. The formed two layers were separated in a separation funnel. The organic layer was extracted, dried over anhydrous sodium sulfate and concentrated. The resulting dark oil was purified by flash chromatography on silica gel to obtain the oil 1-tert-butyl 4-ethyl 4-(2-chloropyridin-4-yl)piperidine-1,4-dicarboxylate (90 g, 32% yield).

Workup

  1. waitThe reaction mixture was kept at 0° C. for 3 hours
  2. customThe formed two layers
  3. customwere separated in a separation funnel
  4. extractionThe organic layer was extracted
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe resulting dark oil was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-ba982221e9d44d6e8fd9dc783b4a4f3e
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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