Water → HCID 68284269, compound

HRID 1527160Notes

Reaction equation

HRID 1527160 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:23]([O:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=1)=[O:24].O>C1COCC1>[N+:32]([C:29]1[CH:28]=[CH:27][C:26]([O:25][C:23]([N:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])=[CH:12]2)=[O:24])=[CH:31][CH:30]=1)([O-:34])=[O:33]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 821294-Nitrophenyl chloroformateHCID 8605861benzyl 1H-indole-3-carboxylate

Product 1

HCID 68284269HCID 68284269, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1H-indole-3-carboxylic acid benzyl ester (100 mg, 0.398 mmol) in dry THF (2 mL) at 0° C. under nitrogen was added NaH (60% in mineral oil, 32 mg, 0.796 mmol). The resulting solution was stirred at 0° C. for 10 min, and added dropwise to a stirred solution of 4-nitrophenyl chloroformate (160 mg, 0.796 mmol) in dry THF (2 mL) cooled at 0° C. The resulting solution was stirred at RT under nitrogen for 48 h. The mixture was poured into water and extracted twice with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude residue was successively purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 7:3) and by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min) to give after extraction of the pure fractions the desired compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.8; MS (LC/MS): 439.0 [M+Na]+; tR (HPLC conditions a): 4.58 min.

Workup

  1. temperaturecooled at 0° C
  2. stirringThe resulting solution was stirred at RT under nitrogen for 48 h
  3. extractionextracted twice with CH2Cl2
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was successively purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 7:3) and by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min)
  8. customto give
  9. extractionafter extraction of the pure fractions the desired compound
  10. custom4.58 min.

Sources & evidence

ORD record
ord-8b571ea39114441899bde844af588649
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…