N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine → [(4-Chloro-thiazol-5-yl)methyl]-isobutyl-piperidin-4-yl-amine

HRID 2111928Notes

Reaction equation

[Li]CCCC.Cl[C:7]1[S:8][C:9]([CH2:13][N:14]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[C:10]([Cl:12])[N:11]=1>O1CCCC1.C([O-])(O)=O.[Na+]>[CH3:23][CH:22]([CH3:24])[CH2:21][N:14]([CH2:13][C:9]1[S:8][CH:7]=[N:11][C:10]=1[Cl:12])[CH:15]1[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]1

Participants

Conditions

Temperature: -78 °C

Procedure

n-BuLi (1.6M in hexanes, 0.50 mL, 0.8 mmol) is added to a cold (−78° C.) solution of (2,4-dichloro-thiazol-5-ylmethyl)-isobutyl-piperdin-4-yl-amine (0.0995 g, 0.3 mmol) in anhydrous tetrahydrofuran. After stirring for 1 h at −78° C., aqueous saturated NaHCO3 is added, then poured in 100 mL aqueous saturated NaHCO3, extracted with ethyl acetate (3×100 mL). The layers are separated and the organic layer dried over Na2SO4, filtered, and concentrated. The crude material is purified on silica gel eluting with 1% NH4OH/10% ethanol/chloroform to yield (0.069 g, 78%) N-(2-methylpropyl)-N-[(4-chloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine: mass spectrum (ion spray): m/z=288.1 (M+1); 1H NMR (CDCl3): δ=8.64 (1H, s), 3.81 (2H, s), 3.16 (2 H, brd), 2.60-2.49 (3H, m), 2.32 (2H, d), 1.82-1.62 (4H, m), 1.53-1.39 (2H, m), 0.91 (6H, d).

Workup

extractionextracted with ethyl acetate (3×100 mL)
customThe layers are separated
dry with materialthe organic layer dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude material is purified on silica gel eluting with 1% NH4OH/10% ethanol/chloroform

Sources & evidence

ORD record: ord-90e4bc138f37415badfe88e9f567d15f
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07521462B2

Reaction notes

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