Tris(1,1-dimethylethyl)phosphine → Ethyl 1-benzyl-4-(4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)phenyl)piperidine-4-carboxylate

HRID 1868814Notes

Reaction equation

HRID 1868814 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]N(C1CCCCC1)C1CCCCC1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.Br[C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][C:48]=1[C:54]#[C:55][C:56]([O:63][CH2:64][CH3:65])([O:60][CH2:61][CH3:62])[O:57][CH2:58][CH3:59]>CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O.C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:47]2[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][C:48]=2[C:54]#[C:55][C:56]([O:57][CH2:58][CH3:59])([O:63][CH2:64][CH3:65])[O:60][CH2:61][CH3:62])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 90423Ethyl 1-benzylpiperidine-4-carboxylateHCID 670999201-Bromo-4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)benzeneHCID 178506922lithium dicyclohexylazanide

Product 1

HCID 67099667Ethyl 1-benzyl-4-(4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)phenyl)piperidine-4-carboxylateYield 38.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

In a glovebox, ethyl 1-benzylpiperidine-4-carboxylate (2.0 g, 8.1 mmol), LiNCy2 (1.55 g, 8.3 mmol), and toluene (10 mL) were loaded sequentially into a 40 mL vial. In a separate vial, Pd(OAc)2 (22 mg, 0.1 mmol), P(t-Bu)3 (44 mg, 0.22 mmol), 1-bromo-4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)benzene (1.5 g, 4.1 mmol), and toluene (10 mL) were loaded sequentially and were then heated at 100° C. for 1 minute. The enolate solution in vial 1 was then added to the reaction mixture in vial 2 via a syringe. The combined mixture was heated at 100° C. for 40 minutes. The reaction mixture was cooled to 23° C. and passed through a short plug of silica gel eluting with EtOAc (20 mL). The filtrate was concentrated in vacuo and purified by silica gel chromatography (eluant: 5-20% EtOAc/hexane+2% TEA), affording 833 mg of ethyl 1-benzyl-4-(4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)phenyl)piperidine-4-carboxylate.

Workup

  1. temperatureThe combined mixture was heated at 100° C. for 40 minutes
  2. temperatureThe reaction mixture was cooled to 23° C.
  3. concentrationThe filtrate was concentrated in vacuo
  4. custompurified by silica gel chromatography (eluant: 5-20% EtOAc/hexane+2% TEA)

Sources & evidence

ORD record
ord-b699dbf5d86b43be859703f2167a570f
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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