Ethyl chloroformate → HCID 86766931, compound

HRID 2410126Notes

Reaction equation

HRID 2410126 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:38])=[C:6]([N:8]2[C:15](=[O:16])[C:14]3[N:13]=[C:12]([C:17]4[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=4)[N:11]([CH:27]([CH3:29])[CH3:28])[C:10]=3[C@H:9]2[C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=2[CH3:37])[CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:49](Cl)(=[O:53])[O:50][CH2:51][CH3:52]>C1COCC1>[CH2:51]([O:50][C:49]([C:9]1([C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=2[CH3:37])[C:10]2[N:11]([CH:27]([CH3:28])[CH3:29])[C:12]([C:17]3[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=3)=[N:13][C:14]=2[C:15](=[O:16])[N:8]1[C:6]1[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[CH3:38])=[O:53])[CH3:52]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86766904HCID 86766904, compound

Product 1

HCID 86766931HCID 86766931, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of the product from example 76 (100 mg, 0.2 mmol) in THF (3 mL) at −78° C. was added NaHMDS (181 μL, 0.2 mmol) and the mixture was stirred at −78° C. for 15 min. Ethyl carbonochloridate (86 μL, 0.9 mmol) was added at −78° C. and the mixture was allowed to warm up to rt and stirred for 1 h. The reaction mixture was quenched with a saturated aqueous NH4Cl solution, then was diluted in EtOAc and extracted with brine. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified by preparative HPLC (Column: Sunfire C18, 30×100 mm, 5 μm. Flow: 30 mL/min. Gradient 5-100% B in 20 min; A=0.1% TFA in water, B═CH3CN). tR: 1.39 min (LC-MS 2); ESI-MS: 624.4/626.4 [M+H]+ (LC-MS 2).

Workup

  1. temperatureto warm up to rt
  2. stirringstirred for 1 h
  3. customThe reaction mixture was quenched with a saturated aqueous NH4Cl solution
  4. additionwas diluted in EtOAc
  5. extractionextracted with brine
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC (Column
  10. waitGradient 5-100% B in 20 min

Sources & evidence

ORD record
ord-5139c965e4364a348d32f4297b758204
Source dataset
uspto-grants-2014_08
Patent number
US08815926B2

Reaction notes

Loading…