2,4-Dinitrobenzoic acid → HCID 59073106, compound

HRID 1837853Notes

Reaction equation

HRID 1837853 reaction equation
[CH:1](=[O:5])/[CH:2]=[CH:3]/[CH3:4].[CH2:6]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=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>[CH2:6]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([C@H:3]([CH3:4])[CH2:2][CH:1]=[O:5])=[CH:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 118802,4-Dinitrobenzoic acidHCID 969131-BenzylindoleHCID 447466Crotonaldehyde3×HCID 103098345-Benzyl-2-tert-butyl-3-methyl-4-imidazolidinone, (2S,5S)-

Product 1

HCID 59073106HCID 59073106, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

Prepared according to the general procedure from crotonaldehyde (125 μL, 1.50 mmol), 1-benzyl-1H-indole (104 mg, 0.500 mmol), 2,4-dinitrobenzoic acid (21.2 mg, 0.100 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-methyl-imidazolidin-4-one (24.6 mg, 0.100 mmol) in CH2Cl2 (0.90 mL) and isopropanol (0.10 mL) at −60° C. for 41 h, at which time an additional 125 μL (1.50 mmol) of crotonaldehyde was added. The reaction was continued for an additional 70 h, at which time an additional 42 μL (0.50 mmol) of crotonaldehyde was added. The reaction was continued at this temperature for an additional 5 h, at which time the temperature was raised to −40° C. for 2 h, then −10° C. for an additional 2 h to provide, after silica gel chromatography (15:85 EtOAc/hexanes), the title compound as a colorless oil (110 mg, 80% yield, 89% ee). IR (film) 3062, 3030, 2965, 2925, 2877, 2820, 2724, 1722, 1613, 1589, 1549, 1496, 1480, 1468, 1452, 1392, 1372, 1356, 1331, 1303, 1251, 1203, 1174, 1017 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.76 (dd, J=2.4, 2.4 Hz, 1H, CHO), 7.66 (dt, J=0.6, 7.5 Hz, 1H, ArH), 7.33-7.08 (m, 8H, ArH), 6.92 (s, 1H, NCH), 5.28 (s, 2H, NCH2), 3.70 (dt, J=6.9, 21 Hz, 1H, ArCH), 2.89 (ddd, J=2.4, 6.6, 16.5 Hz, 1H, CH2CO); 2.72 (ddd, J=1.8, 7.8, 15.9 Hz, 1H, CH2CO); 1.44 (d, J=6.9 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 202.7, 137.5, 131.9, 128.8, 127.6, 126.9, 126.8, 124.6, 122.0, 119.6, 119.3, 119.2, 110.0, 51.2, 50.1, 26.1, 21.0; HRMS (CI) exact mass calcd for (C19H19 NO) requires m/z 277.1467, found m/z 277.1464. [α]D=+3.5 (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 isopropanol/hexanes, 1 mL/min); S isomer tr=26.5 min and R isomer tr=29.5 min.

Workup

  1. customPrepared
  2. waitThe reaction was continued at this temperature for an additional 5 h, at which time
  3. custom−10° C. for an additional 2 h to provide

Sources & evidence

ORD record
ord-0c8761c6f6e64805a39f8e4003205d93
Source dataset
uspto-grants-2004_08
Patent number
US06784323B2

Reaction notes

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