Acetic Acid → 5-Fluoro-3-{4-[4-(6-methoxy-naphthalen-2-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole

HRID 428567Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)[CH:7]=[CH:6]2.CC(O)=O.[F:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[C:27]2[C:33]1[CH2:38][CH2:37][C:36](=O)[CH2:35][CH:34]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCO>[F:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[C:27]2[CH:33]1[CH2:38][CH2:37][CH:36]([N:16]2[CH2:17][CH2:18][N:13]([C:8]3[CH:7]=[CH:6][C:5]4[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=4)[CH:9]=3)[CH2:14][CH2:15]2)[CH2:35][CH2:34]1

Participants

Conditions

Temperature: 23 °C

Procedure

To 400 mg (1.66 mmol) of 1-(6-methoxy-naphthalen-2-yl)-piperazine in 40 mL of CH2Cl2 and 100 mg of glacial HOAc at 23° C. was added 384 mg (1.66 mmol) of 4-(5-fluoro-1H-indol-3-yl)-cyclohex-3-enone followed by 216 mg, (1.89 mmol) of Na(OAc)3BH. After stirring at 23° C. for 12 hours, the reaction mixture was transferred to a separatory funnel and partitioned between water and CH2Cl2. The organics were washed with brine, dried over MgSO4, and chromatographed on silica gel eluting with 20:1 EtOAc:2 M NH3 in MeOH. The product fractions were pooled, stripped, and treated with 115 mg (1.3 mmol) of (CO2H)2 in absolute EtOH to give 640 mg (1.40 mmol, an 84% yield) of the oxalate salt of the title compound as a white crystalline solid. mp: 200-203° C.; MS (ES) m/z 458 (MH)+.

Workup

customthe reaction mixture was transferred to a separatory funnel
custompartitioned between water and CH2Cl2
washThe organics were washed with brine
dry with materialdried over MgSO4
customchromatographed on silica gel eluting with 20:1 EtOAc
customto give 640 mg (1.40 mmol

Sources & evidence

ORD record: ord-862bd1dc56a44f74b307ad1c1ce555de
Source dataset: uspto-grants-2001_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06313126B1

Reaction notes

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