Hydrochloric Acid → (3R,4S)-N-Cyclopropyl-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}-N-[3-(2-methoxyethoxy)-5-(3-methoxypropyl)benzyl]piperidine-3-carboxamide

HRID 658256Notes

Reaction equation

HRID 658256 reaction equation
[CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([O:51][CH2:52][CH2:53][O:54][CH3:55])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:15][CH:14]=3)[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.Cl.O1CCOCC1>C(Cl)Cl>[CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([O:51][CH2:52][CH2:53][O:54][CH3:55])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:15][CH:14]=3)[CH2:11][CH2:10][NH:9][CH2:8]2)=[O:6])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86639854tert-butyl (3R,4S)-3-({cyclopropyl[3-(2-methoxyethoxy)-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)-ethoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 54580283(3R,4S)-N-Cyclopropyl-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}-N-[3-(2-methoxyethoxy)-5-(3-methoxypropyl)benzyl]piperidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution tert-butyl (3R,4S)-3-({cyclopropyl[3-(2-methoxyethoxy)-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)-ethoxy]phenyl}piperidine-1-carboxylate (1 eq.) from the previous step in DCM (0.05 M) was added 4 M HCl in dioxane (10 eq.) and stirred at rt for 5 h. The reaction was concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 5% [2 M NH3 in MeOH] in DCM) to afford the title compound as a colorless oil. 1H NMR (acetone d-6): δ 7.28 (s, 2H), 7.20 (d, 2H), 6.84 (d, 2H), 6.62 (s, 1H), 6.48 (s, 1H), 6.4 (s, 1H), 4.47-4.25 (m, 6H), 4.05 (t, 2H), 3.71 (t, 2H), 3.56 (m, 1H), 3.38 (s, 3H), 3.33 (t, 2H), 3.28 (s, 3H), 3.25 (m, 1H), 3.11 (m, 2H), 2.76 (m, 2H), 2.55 (t, 2H), 2.34 (s, 3H), 2.32 (m, 1H), 1.78 (m, 4H), 0.77 (m, 3H), 0.49 (m, 1H). LRMS [M+H]=699.0

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe crude product was purified by flash column chromatography (SiO2, 5% [2 M NH3 in MeOH] in DCM)

Sources & evidence

ORD record
ord-b4b8fc6c95304cc499185f2bda1758e6
Source dataset
uspto-grants-2011_12
Patent number
US08076359B2

Reaction notes

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