Isopropylamine → 1,1-Dimethylethyl 4-[(4-chlorophenyl)methyl]-4-cyano-1-piperidinecarboxylate

HRID 2401544Notes

Reaction equation

HRID 2401544 reaction equation
C(N)(C)C.C([Li])CCC.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([C:23]#[N:24])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Cl)=[CH:28][CH:27]=1>C1COCC1.O>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20]([CH2:30][C:29]2[CH:32]=[CH:33][C:26]([Cl:25])=[CH:27][CH:28]=2)([C:23]#[N:24])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

7

Reactant 4

HCID 6363IsopropylamineHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 248292211,1-Dimethylethyl 4-[(4-chlorophenyl)methyl]-4-cyano-1-piperidinecarboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of isopropylamine (1.53 ml, 10.94 mmol) in THF (30 ml) at −78° C. was added n-butyllithium (4.38 ml of a 2.5M solution in hexanes, 10.938 mmol). After 10 minutes, a solution of 4-cyanopiperidine-1-carboxylic acid tert-butyl ester in THF (12 ml) was added. After a further 1 hour, a solution of 4-chlorobenzyl chloride (1.84 g, 11.4 mmol) in THF (5 ml) was added and the solution warmed to room temperature over 15 hours. Water (150 ml) was added and the aqueous phase extracted with diethyl ether (150 ml). The organic phase was dried over magnesium sulphate and concentrated to give a crude solid that was purified by recrystallisation from diethyl ether/hexane in two batches to give the product as a white solid (2.650 g, 83%). LC-MS (LCT2) m/z 357 [M+Na+], 235 [M-Boc]+, Rt 8.02 min.

Workup

  1. waitAfter a further 1 hour
  2. extractionthe aqueous phase extracted with diethyl ether (150 ml)
  3. dry with materialThe organic phase was dried over magnesium sulphate
  4. concentrationconcentrated
  5. customto give a crude solid that
  6. customwas purified by recrystallisation from diethyl ether/hexane in two batches

Sources & evidence

ORD record
ord-7c35a66560614a63bd1f3a135ceb16c3
Source dataset
uspto-grants-2014_08
Patent number
US08796293B2

Reaction notes

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