Methyl Bromide → HCID 78097126, compound

HRID 709018Notes

Reaction equation

HRID 709018 reaction equation
[C:1]([C:5]1[CH:24]=[CH:23][C:8]([C:9]([O:11][CH:12]([CH3:22])[CH2:13][N:14]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH3:15])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:25][Br:26]>ClCCCl>[Br-:26].[C:1]([C:5]1[CH:24]=[CH:23][C:8]([C:9]([O:11][CH:12]([CH3:22])[CH2:13][N+:14]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)([CH3:25])[CH3:15])=[O:10])=[CH:7][CH:6]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 6323Methyl Bromide2×HCID 86681547HCID 86681547, compound

Product 1

HCID 78097126HCID 78097126, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of 1-(cyclohexyl(methyl)amino)propan-2-yl 4-(tert-butyl)benzoate (22.5 g, 6.798 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, 2H), 7.57 (d, J=8 Hz, 2H), 5.54-5.51 (m, 1H), 3.93 (dd, J=15, 9 Hz, 1H), 3.63 (d, J=14 Hz, 1H), 3.42-3.36 (m, 1H), 3.05 (s, 6H), 2.23-2.20 (m, 1H), 2.11-2.08 (m, 1H), 1.87-1.83 (m, 2H), 1.57-1.43 (m, 3H), 1.36 (d, J=6 Hz, 3H), 1.30 (s, 9H), 1.23-1.08 (m, 3H); 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) 1.81μ).

Workup

  1. stirringstirred at rt for 8 h
  2. concentrationThe reaction mixture was concentrated
  3. customthe crude material was purified by chromatography on neutral alumina eluting with 2-8% methanol-DCM
  4. customto provide an off white solid
  5. customThe solid material was crystallized from DCM-ether

Sources & evidence

ORD record
ord-60dc5ead5a8143aa87854b151210f4be
Source dataset
uspto-grants-2015_11
Patent number
US09180115B2

Reaction notes

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