反应 #2446089

反应方程式

1-(cyclohexyl(methyl)amino)propan-2-yl 4-(tert-butyl)benzoate

methyl bromide

methyl bromide

→

[2-(4-tert-butyl-benzoyloxy)-propyl]-cyclohexyl-dimethyl-ammonium bromide

溶剂

DCE

反应条件

后处理

1. 1
   workup.STIRRINGstirred at rt for 8 h
2. 2
   浓缩The reaction mixture was concentrated
3. 3
   其他the crude material was purified by chromatography on neutral alumina eluting with 2-8% methanol-DCM
4. 4
   其他to provide an off white solid
5. 5
   其他The solid material was crystallized from DCM-ether

实验过程

To a stirred solution of 1-(cyclohexyl(methyl)amino)propan-2-yl 4-(tert-butyl)benzoate (22.5 g, 67.98 mmol) in DCE (150 ml) was added methyl bromide (25% solution in toluene, 103 ml, 271.90 mmol) and reaction mixture was stirred at rt for 16 h. TLC showed very small amount of unreacted starting material. Hence another 0.5 eq. of methyl bromide was added and stirred at rt for 8 h. The reaction mixture was concentrated and the crude material was purified by chromatography on neutral alumina eluting with 2-8% methanol-DCM to provide an off white solid. The solid material was crystallized from DCM-ether to provide [2-(4-tert-butyl-benzoyloxy)-propyl]-cyclohexyl-dimethyl-ammonium bromide. Yield: 15.5 g (53.5%). 1H NMR (DMSO-d6) δ 7.94 (d, J=8 Hz, 2 H), 7.57 (d, J=8 Hz, 2 H), 5.54-5.51 (m, 1 H), 3.93 (dd, J=15, 9 Hz, 1 H), 3.63 (d, J=14 Hz, 1 H), 3.42-3.36 (m, 1 H), 3.05 (s, 6 H), 2.23-2.20 (m, 1 H), 2.11-2.08 (m, 1 H), 1.87-1.83 (m, 2 H), 1.57-1.43 (m, 3 H), 1.36 (d, J=6 Hz, 3 H), 1.30 (s, 9 H), 1.23-1.08 (m, 3 H); LCMS: m/z=346.4 [M+], RT=3.00 min, (Column: Y, Program: P1). UPLC: 99.90% (200 nm), RT=4.04 min (Mobile Phase A. 0.05% TFA in water, B. Acetonitrile; Column: Zorbax® SB-C18 (4.6×50 mm) 1.8μ).

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