Dichloroacetic Acid → HCID 11211734, compound

HRID 1837857Notes

Reaction equation

HRID 1837857 reaction equation
[Br:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=3)[CH:9]=[C:8]2[CH3:18])=[CH:4][CH:3]=1.ClC(Cl)C(O)=O.[CH2:27]([C@@H:34]1N[C@H](C(C)(C)C)N(C)[C:35]1=[O:44])[C:28]1C=CC=CC=1.C(=O)/C=C/C>C(O)(C)C.C(Cl)Cl>[Br:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=3)[C:9]([C@H:27]([CH3:28])[CH2:34][CH:35]=[O:44])=[C:8]2[CH3:18])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6597Dichloroacetic AcidHCID 447466CrotonaldehydeHCID 103098345-Benzyl-2-tert-butyl-3-methyl-4-imidazolidinone, (2S,5S)-HCID 11278924HCID 11278924, compound

Product 1

HCID 11211734HCID 11211734, compoundYield 420.1%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

To 1-(4-bromo-benzyl)-5-methoxy-2-methyl-1H-indole (110 mg, 0.333 mmol) in a 2-dram amber vial was added CH2Cl2 (0.60 mL), isopropanol (0.066 mL), dichloroacetic acid (5.5 μL, 0.066 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (16.4 mg, 0.066 mmol). This solution was stirred for 10 min at room temperature, then placed in a −70° C. bath for an additional 10 min. At this time, crotonaldehyde (82 μL, 1.0 mmol) was added and the reaction was stirred at −70° C. for 9 h. The reaction mixture was then transferred cold through a silica plug into a flask and concentrated to provide, after silica gel chromatography (20:80 EtOAc/hexanes), the title compound as a colorless oil (111 mg, 84% yield, 87% ee). IR (film) 2930, 2823, 2730, 1722, 1618, 1581, 1530, 1483, 1452, 1405, 1229, 1156, 1073, 1037, 1011, 902, 798, 476 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.69 (dd, J=1.8, 1.8 Hz, 1H, CHO), 7.38 (dt, J=2.4, 9.0 Hz, 2H, ArH), 7.12 (d, J=2.1 Hz, 1H, ArH), 7.05 (d, J=9.0, 1H, ArH), 6.79-6.75 (m, 3H, ArH), 5.19 (s, 2H NCH2), 3.88 (s, 3H, OCH3), 3.66 (dt, J=7.2, 22.2 Hz, 1H ArCH), 3.02 (ddd, J=1.8, 8.1, 16.5 Hz, 1H, CH2CO); 2.85 (ddd, J=2.1, 6.6, 16.5 Hz, 1H, CH2CO); 2.30 (s, 3H, ArCH3) 1.48 (d, J=7.2 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 202.5, 153.6, 137.0, 132.7, 132.0, 131.9, 127.6, 126.6, 121.1, 114.5, 110.0, 109.8, 102.3, 56.2, 50.6, 46.2, 26.4, 21.4, 10.9; HRMS (CI) exact mass calcd for (C21H22BrNO2) requires m/z 399.0834, found m/z 399.0833. [α]D=−20.8 (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 OD-H and OD guard column (4:96 ethanol/hexanes, 1 mL/min); S isomer tr=45.1 min and R isomer tr=35.9 min.

Workup

  1. customplaced in a −70° C.
  2. customfor an additional 10 min
  3. stirringthe reaction was stirred at −70° C. for 9 h
  4. concentrationconcentrated
  5. customto provide

Sources & evidence

ORD record
ord-f40a8e8372b245a59e99f36e3cc67798
Source dataset
uspto-grants-2004_08
Patent number
US06784323B2

Reaction notes

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