Formamide → (1R,4R)-N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-formamide

HRID 2193990Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=O)[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:20]([NH2:22])=[O:21]>C(O)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[C:18]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C@H:12]([NH:22][CH:20]=[O:21])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 162.5 °C

Procedure

(R)-4-(3,4-dichlorophenyl)-3,4-dihydro-1-naphthalenone (1.2 g) was added formic acid (3 mL) and formamide (3 mL). The reaction mixture was heated to 160-165° C. for 15 h under nitrogen atmosphere. The reaction mixture was cooled to rt and decanted the solvent. The residue solids was passed through flash column using EtOAc:Hexane (3:7 to 1:1) to give and (1R,4R)—Norsertralaine formamide (400 mg, first spot), and (1S,4R)—Norsertraline formamide (360 mg). 1H NMR of the first product [(1R,4R)-isomer]: (CDCl3) δ 1.80-2.10 (m, 3H), 2.10-2.20 (m, 1H), 4.00-4.10 (m, 1H), 5.22-5.30 (m, 1H), 6.10-6.20 (m, 1H), 6.80-6.90 (M, 1H), 6.90-6.96 (m, 1H), 7.10-7.40 (m, 5H), 8.22 (s, 1H). M+320. 1H NMR of the second product [(1S,4R)-isomer: δ 1.64-1.90 (m, 2H), 2.10-2.28 (m, 2H), 4.10 (m, 1H), 5.38-5.42 (m, 1H), 5.82-6.05 (m, 1H), 6.80-6.90 (m, 2H), 7.10-40 (m, 5H), 8.28 (s, 1H). Mass Spec. M+320.

Workup

temperatureThe reaction mixture was cooled to rt
customdecanted the solvent
customto give

Sources & evidence

ORD record: ord-48cd7338e8f04ff981f8da6d1cdf17cf
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329950B2

Reaction notes

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