Triethylamine → 3-(4-Ethoxy-2-oxocyclohex-3-enyl)propyl-7-methoxy-2-oxo-2h-chromen-3-ylcarbamate

HRID 1593221Notes

Reaction equation

HRID 1593221 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[C:8](C(O)=O)[C:9](=[O:13])[O:10]2)=[CH:5][CH:4]=1.CC[N:19]([CH2:22]C)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:31])=CC=1.[CH2:41]([O:43][C:44]1[CH2:49][CH2:48][CH:47]([CH2:50][CH2:51][CH2:52][OH:53])[C:46](=[O:54])[CH:45]=1)[CH3:42]>C1C=CC=CC=1.O>[CH2:41]([O:43][C:44]1[CH2:49][CH2:48][CH:47]([CH2:50][CH2:51][CH2:52][O:53][C:22](=[O:31])[NH:19][C:8]2[C:9](=[O:13])[O:10][C:11]3[C:6]([CH:7]=2)=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=3)[C:46](=[O:54])[CH:45]=1)[CH3:42]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 5839417-Methoxycoumarin-3-carboxylic AcidHCID 252417513-Ethoxy-6-(3-hydroxypropyl)cyclohex-2-enone

Product 1

HCID 589993283-(4-Ethoxy-2-oxocyclohex-3-enyl)propyl-7-methoxy-2-oxo-2h-chromen-3-ylcarbamateYield 50%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 7-methoxy-3-carboxycoumarin (335 mg, 1.5 mmol), NEt3 (1.05 mL, 7.6 mmol) and DPPA (0.36 mL, 1.7 mmol) in benzene (15 mL) was stirred at 65° C. for 4 h. A solution of 3 (260 mg, 1.3 mmol) in benzene (2 mL) was then added and the mixture stirred at 65° C. for 16 h. Upon cooling, water (40 mL) was added and the mixture extracted with DCM (3×40 mL). The combined organic phases were washed with sat. NaHCO3 (30 mL), brine (30 mL), dried over anhydrous MgSO4 and reduced to dryness. The resultant solid was purified by flash column chromatography (×2, gradient elution with DCM/EtOAC (8/2) to DCM/EtOAc/MeOH (8/1/1), and then DCM/MeOH (9/1)) to yield 5 as an off-white solid (270 mg, 49.5%). Rf 0.63 (hexanes/EtOAc 1/2); Mp. 131-134° C.; 1H NMR (300 MHz, CDCl3) δ 8.22 (1H, s), 7.34 (2H, m), 6.84 (1H, dd, J=8.6 Hz, 2.4 Hz), 6.79 (1H, d, J=2.4 Hz), 5.29 (1H, s), 4.18 (2H, t, J=6.3 Hz), 3.85 (2H, 2q, J=7.0 Hz), 3.82 (3H, s), 2.42 (2H, 2d, J=7.1 Hz), 2.22 (1H, m), 2.08 (1H, dq, J=14.2 Hz, 5.0 Hz), 1.94-1.85 (1H, m), 1.78-1.66 (3H, m), 1.52-1.42 (1H, m), 1.33 (3H, t, J=7.0 Hz); 13C NMR (75 MHz, CDCl3) δ 201.0, 176.9, 161.1, 158.9, 153.6, 151.3, 128.4, 122.0, 121.9, 113.3, 113.2, 102.4, 100.8, 66.0, 64.4, 55.9, 44.9, 28.3, 26.6 (×2), 26.2, 14.3; ESI MS m/z 438 (M++Na+).

Workup

  1. temperatureUpon cooling
  2. extractionthe mixture extracted with DCM (3×40 mL)
  3. washThe combined organic phases were washed with sat. NaHCO3 (30 mL), brine (30 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. customThe resultant solid was purified by flash column chromatography (
  6. wash×2, gradient elution with DCM/EtOAC (8/2) to DCM/EtOAc/MeOH (8/1/1)

Sources & evidence

ORD record
ord-c6d639ee8d65483081274fbb5e981522
Source dataset
uspto-grants-2007_11
Patent number
US07294748B2

Reaction notes

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