Indole → HCID 59073101, compound

HRID 1837851Notes

Reaction equation

HRID 1837851 reaction equation
[CH:1](=[O:5])/[CH:2]=[CH:3]/[CH3:4].[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1.[N+](C1C=C([N+]([O-])=O)C=CC=1C(O)=O)([O-])=O.C([C@@H]1N[C@H](C(C)(C)C)N(C)C1=O)C1C=CC=CC=1>C(Cl)Cl.C(O)(C)C>[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([C@H:3]([CH3:4])[CH2:2][CH:1]=[O:5])=[CH:7]1

Participants

7

Reactant 4

HCID 798IndoleHCID 118802,4-Dinitrobenzoic acidHCID 447466Crotonaldehyde2×HCID 103098345-Benzyl-2-tert-butyl-3-methyl-4-imidazolidinone, (2S,5S)-

Product 1

HCID 59073101HCID 59073101, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

Prepared according to general procedure from crotonaldehyde (100 μL, 1.25 mmol), indole (146 mg, 1.25 mmol), 2,4-dinitrobenzoic acid (53 mg, 0.25 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (62 mg, 0.25 mmol) in CH2Cl2 (2.25 mL) and isopropanol (0.25 mL) at −60° C. for 19 h at which time an additional 30 μL (0.36 mmol) of crotonaldehyde was added. The reaction was allowed to continue stirring for an additional 3 h to provide, after silica gel chromatography (20:80 EtOAc/hexanes), the title compound as a colorless oil (168 mg, 72% yield, 91% ee). IR (film) 3408, 2962, 2875, 2833, 2729, 1716, 1617, 1451, 1420, 1337, 1223, 1099, 1010, 772, 741 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.77 (dd, J=2.1, 2.1 Hz, 1H, CHO), 8.15 (s, 1H, NH), 7.68 (dt, J=0.6, 7.8 Hz, 1H, ArH), 7.35 (dt, J=1.5, 7.8 Hz, 1H, ArH), 7.27-7.15 (m, 2H, ArH), 6.94 (d, J=2.4 Hz, 1H, NCH), 3.68 (dt, J=7.2, 21 Hz, 1H, ArCH), 2.91 (ddd, J=2.4, 6.9, 16.2 Hz, 1H, CH2CO); 2.73 (ddd, J=2.1, 7.2, 16.2 Hz, 1H, CH2CO); 1.47 (d, J=6.9 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 203.0, 136.5, 126.1, 122.1, 120.7, 120.1, 119.3, 118.9, 111.4, 50.9, 26.0, 21.6; HRMS (CI) exact mass calcd for (C12H13NO) requires m/z 187.0997, found m/z 153.0993. [α]D=−2.2 (c=CHCl3). The enantiomeric ratio was determined by HPLC analysis of the alcohol, obtained by NaBH4 reduction of the aldehyde, using a Chiracel OD-H and OD guard column (10:90 ethanol/hexanes, 1 mL/min); S isomer tr=20.2 min and R isomer tr=17.6 min.

Workup

  1. customPrepared
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Sources & evidence

ORD record
ord-3f45e856cf604cbe86311236b4e6cd57
Source dataset
uspto-grants-2004_08
Patent number
US06784323B2

Reaction notes

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