Trifluoroacetic acid → (3R)-(-)-3-(1-Methyl-1H-indol-3-yl)butyraldehyde

HRID 1837845Notes

Reaction equation

HRID 1837845 reaction equation
[CH:1](=[O:5])/[CH:2]=[CH:3]/[CH3:4].[CH3:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1.C(O)(C(F)(F)F)=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.C1C=CC=CC=1>[CH3:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C@H:3]([CH3:4])[CH2:2][CH:1]=[O:5])=[CH:8]1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 117811-MethylindoleHCID 447466CrotonaldehydeHCID 103098345-Benzyl-2-tert-butyl-3-methyl-4-imidazolidinone, (2S,5S)-

Product 1

HCID 9899133(3R)-(-)-3-(1-Methyl-1H-indol-3-yl)butyraldehydeYield 82.5%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

Prepared according to the general procedure from (E)-crotonaldehyde (125 μL, 1.50 mmol), 1-methyl-1H-indole (64 μL, 0.50 mmol), TFA (7.7 μL, 0.10 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (24.6 mg, 0.100 mmol) in CH2Cl2 (0.85 mL) and isopropanol (0.15 mL) at −83° C. for 19 h to provide, after silica gel chromatography (benzene), the title compound as a colorless oil (83 mg, 82% yield, 92% ee). IR (film) 3054, 2960, 2824, 2722, 1720, 1616, 1550, 1474, 1374, 1329, 1241, 740 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.75 (dd, J=2.1, 2.1 Hz, 1H, CHO), 7.63 (d, J=7.8 Hz, 1H, ArH), 7.32-7.21 (m, 2H, ArH), 7.12 (ddd, J=1.5, 7.4, 8.1 Hz, 1H, ArH), 6.84 (s, 1H, NCH), 3.75 (s, 3H, NCH3), 3.68 (dt, J=6.9, 13.8 Hz, 1H, ArCH), 2.88 (ddd, J=2.7, 6.9, 16.2 Hz, 1H, CH2CO); 2.71 (ddd, J=2.7, 6.9, 16.2 Hz, 1H, CH2CO); 1.44 (d, J=7.2 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 202.8, 137.2, 126.6 125.2, 121.8, 119.1, 118.9, 118.8, 109.5, 51.2, 32.8, 26.0, 21.9; HRMS (CI) exact mass calcd for (C13H15NO) requires m/z 201.1154, found m/z 201.1152. [α]D−−4.2 (c=1.0, CHCl3). The enantiomeric ratio was determined by HPLC analysis of the alcohol, obtained by NaBH4 reduction of the aldehyde, using a Chiracel AD and AD guard column (2:98 ethanol/hexanes, 1 mL/min); S isomer tr=25.2 min and R isomer tr=27.8 min.

Workup

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Sources & evidence

ORD record
ord-475c1519172a4a84afd16bf320321ba8
Source dataset
uspto-grants-2004_08
Patent number
US06784323B2

Reaction notes

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