Dimethylamine → (2S,4R)-4-Cyclohexyl-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine

HRID 571172Notes

Reaction equation

HRID 571172 reaction equation
C=CC.[CH3:4][NH:5][CH3:6].CC1C=CC(S(O[C@@H:18]2[CH2:27][C@H:26]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19]2)(=O)=O)=CC=1>>[CH:28]1([C@@H:26]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][C@@H:18]([N:5]([CH3:6])[CH3:4])[CH2:27]2)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[CH:28]1([C@@H:26]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH2:27]2)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1

Participants

5

Reactant 3

HCID 674DimethylamineHCID 8252PropyleneHCID 86666517(2R,4R)-4-Cyclohexyl-1,2,3,4-tetrahydronaphthalen-2-yl 4-methylbenzenesulfonate

Product 2

HCID 66647021(2S,4R)-4-Cyclohexyl-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amineHCID 86666518(R)-1-cyclohexyl-1,2-dihydronaphthalene

Conditions

Temperature
83 °C

Procedure

(Bosse K, Marineau J, Nason D M, Fliri A J, Segelstein B E, Desai K, and Volkmann R A (2006) Expanding the medicinal chemistry toolbox: stereospecific generation of methyl group-containing propylene linkers. Tetrahedron Letters 47:7285-7287) Dimethylamine (40% in H2O, 6 mL) and (2R,4R)-4-cyclohexyl-1,2,3,4-tetrahydronaphthalen-2-yl 4-methylbenzenesulfonate 3a (0.19 g, 0.5 mmol) were placed in a tube, sealed, and heated at 83° C. for 24 hours. The solvent was removed and the crude material was purified by column chromatography (Si-gel) to give 4a in a 70% yield and 5a, (30%, (R)-1-cyclohexyl-1,2-dihydronaphthalene). After bench chromatography, 4a was examined using chiral (RegisCell™, EtOH(15):hexanes(85)) HPLC technology to indicate ee above 98% by UV trace. 1H NMR (CDCl3) 1.00-1.31 (m, 5H), 1.39-1.47 (m, 1H), 1.57-1.85 (m, 6H), 2.48-2.52 (m, 1H), 2.72-2.77 (m, 1H), 2.80 (s, 6H), 3.03 (dd, J=9.0, 16.6 Hz, 1H), 3.34 (dd, J=6.8, 16.0 Hz, 1H), 3.72-3.75 (m, 1H), 7.09-7.29 (m, 4H). 13C NMR (CDCl3) 26.5, 26.8, 27.3, 30.2, 31.8, 32.3, 41.6, 41.9, 43.5, 56.8, 124.9, 125.7, 129.1, 129.2, 136.0, 139.7. HRMS m/z Calcd for C18H27N 258.2216 [M+H]+. Found 258.2220. For pharmacological studies, the free base was converted to the HCl salt; MP: 174-176° C. Anal. Calcd for C18H27N+HCl+H2O: C, 69.32; H, 9.70; N, 4.49. Found: C, 69.48; H, 9.98; N, 4.34.

Workup

  1. customsealed
  2. customThe solvent was removed
  3. customthe crude material was purified by column chromatography (Si-gel)

Sources & evidence

ORD record
ord-ae6bea672e6a4cfb88ea3a8d16673db6
Source dataset
uspto-grants-2015_05
Patent number
US09024071B2

Reaction notes

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