Formaldehyde → HCID 24857671, compound

HRID 556144Notes

Reaction equation

HRID 556144 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH:11]([NH:19][CH3:20])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH2:21]=O>C(O)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH:11]([N:19]([CH3:21])[CH3:20])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 24857670HCID 24857670, compound2×

Product 1

HCID 24857671HCID 24857671, compound

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

Referring to Scheme 1, the beta-tetralone analog 5 is derived from the alpha-tetralone 1 in four steps. The reduced ketone (Compound 2) is dehydrated and the resultant alkene (Compound 3) is converted to the diol (Compound 4). Elimination of water from the diol gives the beta-tetralone (Compound 5). Compound 5 is then condensed with ammonium chloride under reductive amination conditions to give Compound 6, a compound of the invention (e.g., using the preferred 3,4-dichorophenyl as an example, to give [4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-amine). Alternatively, compound 5 is condensed with methylamine hydrochloride under the same conditions to give a compound of the invention, [4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-methyl-amine (Compound 7). Additionally, the monomethyl amine (Compound 7) can be further elaborated under Eschweiler-Clark conditions (using formic acid (HCO2H) and formaldehyde (HCHO)) to give a compound of the invention, [4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-dimethyl-amine (Compound 8). Compounds 6, 7, or 8 may be synthesized as a mixture of racemic cis and trans, or may be separated to give an enantiomerically enriched or an enantiomerically pure form of one of its four isomers. Cis and trans assignments may be made using methods known in the art (e.g., on the basis of NMR coupling patterns). The absolute configuration can, for instance, be determined by synthesis from a precursor of known configuration, or by X-ray crystallographic determination using a suitable crystal of the compound.

Sources & evidence

ORD record
ord-87875fa67dc84d0196e69b16a7d4b035
Source dataset
uspto-grants-2011_11
Patent number
US08053603B2

Reaction notes

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