Ethyl chloroformate → HCID 68109201, compound

HRID 2179365Notes

Reaction equation

HRID 2179365 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([S:10]([C:13]3[CH:14]=[C:15]([OH:33])[C:16]4[O:25][C:24]5[CH2:23][CH2:22][N:21]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:20][C:19]=5[C:17]=4[CH:18]=3)(=[O:12])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[Na+].Cl[C:37]([O:39][CH2:40][CH3:41])=[O:38]>O.ClCCl>[CH2:40]([O:39][C:37]([N:1]1[C:9]2[C:4](=[CH:5][C:6]([S:10]([C:13]3[CH:14]=[C:15]([OH:33])[C:16]4[O:25][C:24]5[CH2:23][CH2:22][N:21]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[CH2:20][C:19]=5[C:17]=4[CH:18]=3)(=[O:12])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)=[O:38])[CH3:41]

Participants

6

Reactant 3

HCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 68109648HCID 68109648, compound

Product 1

HCID 68109201HCID 68109201, compoundYield 29.2%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of the product of step B (90 mg, 0.19 mmol), sodium hydroxide (31 mg, 0.76 mmol) tetrabutylammonium hydrogen sulfate (13 mg, 0.04 mmol) and water (2 drops) in dichloromethane (10 mL) was stirred at ambient temperature for 5 min under an argon atmosphere before addition of ethyl chloroformate (24 μL, 0.25 mmol). The reaction mixture was stirred for 2 h before quenching with aqueous ammonium chloride (15 mL) and extracted with dichloromethane. The organic extract was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 30:70 hexane/ethyl acetate) to give tert-butyl 8-((1-(ethoxycarbonyl)-1H-indol-5-yl)sulfonyl)-6-hydroxy-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (30 mg, 29%) as a yellow solid: 1H NMR (CDCl3, 400 MHz) δ 8.25 (d, J=8.8 Hz, 1H), 8.20 (s, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.78-7.52 (m, 2H), 7.43 (d, J=1.6 Hz, 1H), 6.70-6.63 (m, 1H), 4.54 (s, 2H), 4.50 (q, J=7.2 Hz, 2H), 3.89-3.72 (m, 2H), 2.91-2.77 (m, 2H), 1.51 (s, 9H), 1.46 (t, J=7.2 Hz, 3H).

Workup

  1. custombefore quenching with aqueous ammonium chloride (15 mL)
  2. extractionextracted with dichloromethane
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (SiO2, 30:70 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e8d0abdc7baf417d89645e39c3e6addc
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

Loading…