Trifluoroacetic acid → HCID 86588401, compound

HRID 1837849Notes

Reaction equation

HRID 1837849 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]=[CH:11][CH:12]=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:14][N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16]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>[CH2:1]([O:8][CH2:9][C@@H:10]([C:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:15]([CH3:14])[CH:16]=1)[CH2:11][CH:12]=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 117811-MethylindoleHCID 103098345-Benzyl-2-tert-butyl-3-methyl-4-imidazolidinone, (2S,5S)-HCID 566166104-(Benzyloxy)but-2-enal

Product 1

HCID 86588401HCID 86588401, compoundYield 87.2%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

Prepared according to the general procedure from 4-benzyloxy-but-2-enal (286 mg, 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-imidazolidm-4-one (24.6 mg, 0.100 mmol) in CH2Cl2 (0.85 mL) and isopropanol (0.15 mL) at −83° C. for 18.5 h to provide, after silica gel chromatography (50:50 Et2O/hexanes), the title compound as a colorless oil (134 mg, 84% yield, 96% ee). IR (film) 3056, 2957, 2894, 2830, 2722, 1717, 1618, 1600, 1582, 1550, 1478, 1451, 1370, 1331, 1309, 1272, 1223, 1173, 1110, 1070, 1024, 772, 740, 714 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.77 (dd, J=2.1, 2.1 Hz, 1H, CHO), 8.04 (d, J=7.2 Hz, 2H, ArH), 7.75 (d, J=8.1 Hz, 1H, ArH), 7.61-724 (m, 5H, ArH), 7.17 (ddd, J=1.5, 6.6, 8.1 Hz, 1H, ArH), 6.96 (s, 1H, NCH), 4.73 (dd, J=5.1, 11.1 Hz, 1H, CH2O). 4.42 (dd, J=8.7, 11.1 Hz, 1H, CH2O), 4.12 (m, 1H, ArCH), 3.76 (s, 3H, NCH3), 3.06 (ddd, J=2.1, 6.3, 16.8 Hz, 1H, CH2CO); 2.96 (ddd, J=2.7, 8.4, 16.8 Hz, 1H, CH2CO); 13C NMR (75 MHz, CDCl3) δ 201.5, 166.4, 137.1, 133.1, 129.9, 129.6, 128.5, 126.8, 126.4, 122.1, 119.3, 119.0, 112.9, 109.6, 68.1, 46.5, 33.0, 31.2; HRMS (CI) exact mass calcd for (C20H19NO) requires m/z 321.1365, found m/z 321.1354. [α]D=−2.0 (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 AS and AS guard column (4:96 ethanol/hexanes, 1 mL/min); S isomer tr=42.9 min and R isomer tr=53.2 min.

Workup

  1. customPrepared
  2. customto provide

Sources & evidence

ORD record
ord-dde01546a11e4ed7ab7756c32e9a66c4
Source dataset
uspto-grants-2004_08
Patent number
US06784323B2

Reaction notes

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