Ammonium Chloride → Tert-butyl 4-cyano-4-(cyclopropylmethyl)piperidine-1-carboxylate

HRID 502890Notes

Reaction equation

HRID 502890 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:27][CH:28]1[CH2:30][CH2:29]1.[NH4+].[Cl-]>C1COCC1>[C:1]([C:3]1([CH2:27][CH:28]2[CH2:30][CH2:29]2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81503BromomethylcyclopropaneHCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 57425738Tert-butyl 4-cyano-4-(cyclopropylmethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl 4-cyanopiperidine-1-carboxylate I-1 (1.0 g, 4.8 mmol) in THF (20 mL) at room temperature was treated with KHMDS (9.6 mL of a 1.0 M solution in TBF, 9.6 mmol). After 30 min, (bromomethyl)cyclopropane (0.47 mL, 4.8 mmol) was added dropwise and the mixture was stirred until LCMS indicated the reaction was complete. The reaction mixture was poured into saturated aqueous NH4Cl (50 nil) and extracted with EtOAc (3×50 mL), and the combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to afford tert-butyl 4-cyano-4-(cyclopropyl-methyl)piperidine-1-carboxylate (I-2, M+H+=265.2). This material was used in subsequent reactions without further purification.

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. dry with materialthe combined organic extracts were dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c8ed0a5fe93e4575b693e78ee3f4ed96
Source dataset
uspto-grants-2010_08
Patent number
US07776886B2

Reaction notes

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