Ethyl chloroformate → 1477492-01-5

HRID 1404830Notes

Reaction equation

HRID 1404830 reaction equation
[F:1][C:2]1[C:7]([NH2:8])=[C:6]([N+:9]([O-])=O)[CH:5]=[CH:4][C:3]=1[NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1.[Cl-].[NH4+].CCN(C(C)C)C(C)C.Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34]>CO.[Zn]>[NH2:8][C:7]1[C:2]([F:1])=[C:3]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH:4]=[CH:5][C:6]=1[NH:9][C:33](=[O:34])[O:35][CH2:36][CH3:37]

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 86700475HCID 86700475, compound

Product 1

HCID 718122401477492-01-5Yield 27.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of compound 3 (0.800 g, 2.86 mmol, 1.00 equiv) in methanol (7.2 mL) was added zinc powder (0.930 g, 14.3 mmol, 5.00 equiv) followed by ammonium chloride solution (0.760 g, 14.3 mmol, 5.00 equiv) dropwise. After being stirred at RT for 5 h, DIPEA (0.460 g, 3.58 mmol, 1.25 equiv) and ethyl chloroformate (0.310 g, 2.87 mmol, 1.00 equiv) were added to reaction mixture at 10° C. and the stirring was continued for another 3 h at RT. After consumption of the starting material (by TLC), the reaction mixture was diluted with water (24 mL) and stirred for 1 h to give the solid. The obtained solid was filtered, dissolved in EtOAc (15 mL) and again filtered the un-dissolved solid. The filtrate was evaporated and recrystallized using n-hexane to afford compound 1A (0.250 g, 27.0%) as brown solid. TLC: 50% EtOAc/Hexane (Rf: 0.20) 1H NMR (500 MHz, CDCl3): δ 7.31 (t, J=7.5 Hz, 2H), 7.02 (t, J=6.8 Hz, 2H), 6.75 (d, J=6.8 Hz, 1H), 6.07 (t, J=6.8 Hz, 1H), 4.31 (s, 2H), 4.22-4.18 (m, 3H), 3.84 (br s, 2H, Exc), 1.29 (t, J=5.6 Hz, 3H); UPLC purity: 91.0%; LC-MS: m/z=322 (M+-1) at RT 3.37 (82.8%)

Workup

  1. waitthe stirring was continued for another 3 h at RT
  2. customAfter consumption of the starting material (by TLC)
  3. additionthe reaction mixture was diluted with water (24 mL)
  4. stirringstirred for 1 h
  5. customto give the solid
  6. filtrationThe obtained solid was filtered
  7. dissolutiondissolved in EtOAc (15 mL)
  8. filtrationagain filtered the un-dissolved solid
  9. customThe filtrate was evaporated
  10. customrecrystallized

Sources & evidence

ORD record
ord-4697d7b7d6c841c19f028022afec529d
Source dataset
uspto-grants-2014_12
Patent number
US08916133B2

Reaction notes

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