Benzyl Chloride → tert-Butyl 4-[4-(3-phenylprop-1-yn-1-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate

HRID 549943Notes

Reaction equation

[CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:49]([C:51]1[N:52]=[C:53]([CH:56]2[CH2:61][CH2:60][N:59]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:58][CH2:57]2)[S:54][CH:55]=1)#[CH:50]>O1CCCC1.CC#N.CC#N.Cl[Pd]Cl>[C:2]1([CH2:1][C:50]#[C:49][C:51]2[N:52]=[C:53]([CH:56]3[CH2:61][CH2:60][N:59]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:58][CH2:57]3)[S:54][CH:55]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Under argon, benzyl chloride (134 mg), bis(acetonitrile)dichloropalladium(II) (5.5 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (30 mg) and caesium carbonate (363 mg) are added to a degassed solution of tert-butyl 4-(4-ethynyl-1,3-thiazol-2-yl)piperidine-1-carboxylate (X-1, 310 mg) in tetrahydrofuran (4 ml). The mixture is then warmed to 65° C. After subsequent cooling, the catalyst is removed by filtration over Celite and the filtrate is concentrated under reduced pressure. After chromatographic purification, this gives tert-butyl 4-[4-(3-phenylprop-1-yn-1-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate (329 mg).

Workup

customAfter subsequent cooling, the catalyst is removed by filtration over Celite
concentrationthe filtrate is concentrated under reduced pressure
customAfter chromatographic purification

Sources & evidence

ORD record: ord-f27863ca975b410eb1406fdd5eb099bd
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07943774B2

Reaction notes

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