Ammonium Chloride → (+)-N,N-diethyl-4-[{[(S)-(4-methylphenyl)sulfinyl]amino}(8-quinolinyl)methyl]-benzamide

HRID 30497

Reaction equation

[CH2:1]([N:3]([CH2:13][CH3:14])[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)[CH3:2].[Li]CCCC.[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([S@@:27](/[N:29]=[CH:30]/[C:31]2[CH:32]=[CH:33][CH:34]=[C:35]3[C:40]=2[N:39]=[CH:38][CH:37]=[CH:36]3)=[O:28])=[CH:23][CH:22]=1.[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1COCC1.C1(C)C=CC=CC=1>[CH2:1]([N:3]([CH2:13][CH3:14])[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([CH:30]([NH:29][S@:27]([C:24]2[CH:23]=[CH:22][C:21]([CH3:20])=[CH:26][CH:25]=2)=[O:28])[C:31]2[CH:32]=[CH:33][CH:34]=[C:35]3[C:40]=2[N:39]=[CH:38][CH:37]=[CH:36]3)=[CH:7][CH:6]=1)[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

N,N-diethyl 4-iodo-benzamide (3.1 g, 10 mmol) was dissolved in dry toluene/THF (9:1, 200 mL) and cooled to −78° C. under nitrogen. n-BuLi (7.8 mL, 1.3 M in hexane, 10 mmol) was added dropwise during 5 to 10 min. After further 5 min, 3 (1.0 g, 3.4 mmol) was added dissolved in toluene (1 mL). The solution was stirred 10 min, then NH4Cl (aq.) was added. Concentration, aqueous workup and chromatography on silica gave a total of 0.70 g (44%) of a 70:30 mixture of diastereomers. The pure major isomer 5 (0.37 g) was obtained by one more chromatography. 1H NMR (CDCl3): δ1.2 (m, 6H), 2.4 (s, 3H), 3.4 (m, 4H), 6.35 (d, J=7.5 Hz, 1 H), 6.61 (d, J=7.5 Hz,1 H), 7.15-7.55 (m, 11H), 7.75 (m, 1H), 8.12 (m, 1H), 8.75 (m, 1H).

Workup

concentrationConcentration, aqueous workup and chromatography on silica
customgave
additiona total of 0.70 g (44%) of a 70:30 mixture of diastereomers

Sources & evidence

ORD record: ord-6e3ffd5e9a7547cc853c664e0f6bfd9f
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07423154B2

Linked notes

Loading…