Ethyl chloroformate → HCID 72193259, compound

HRID 1404837Notes

Reaction equation

HRID 1404837 reaction equation
[F:1][C:2]1[C:7]([NH2:8])=[C:6]([N+:9]([O-])=O)[CH:5]=[C:4]([F:12])[C:3]=1[NH:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1.[Cl-].[NH4+].CCN(C(C)C)C(C)C.Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35]>CO.[Zn]>[NH2:8][C:7]1[C:2]([F:1])=[C:3]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[C:4]([F:12])=[CH:5][C:6]=1[NH:9][C:34](=[O:35])[O:36][CH2:37][CH3:38]

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 86700479HCID 86700479, compound

Product 1

HCID 72193259HCID 72193259, compoundYield 23.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of compound 3 (0.062 g, 0.21 mmol, 1.0 equiv) in methanol (0.560 mL) was added zinc powder (0.068 g, 1.04 mmol, 5.00 equiv) followed by ammonium chloride solution (55.3 mg, 1.04 mmol, 5.00 equiv) drop wise. After being stirred for 4 h at RT, DIPEA (48.0 μL, 0.260 mmol, 1.25 equiv) and ethyl chloroformate (20.0 μL, 0.210 mmol, 1.00 equiv) were added to reaction mixture at 10° C. and the stirring was continued for another 2 h at RT. After consumption of the starting material (by TLC), the reaction mixture was diluted with water (25 mL) and extracted with EtOAc (2×75 mL). The separated organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude; which was purified by neutral alumina column chromatography (EtOAc/Hexane 18:82) to afford to compound 4A (0.017 g, 21%) as an off-white solid. TLC: 50% EtOAc/Hexane (Rf: 0.50); 1H NMR (500 MHz, CDCl3): δ 7.30-7.27 (m, 2H), 7.00 (t, J=8.5 Hz, 2H), 6.88 (d, J=11.5 Hz, 1H), 6.26 (br s, 1H, Exc), 4.40 (d, J=6.0 Hz, 2H), 4.21 (q, J=7.0 Hz, 2H), 3.75 (br s, 1H, Exc), 3.50 (s, 2H, Exc), 1.30 (t, J=7.0 Hz, 3H); LC-MS: m/z=340 (M++1) at RT 3.46 (94.3% purity); UPLC purity: 95.2%

Workup

  1. waitthe stirring was continued for another 2 h at RT
  2. customAfter consumption of the starting material (by TLC)
  3. additionthe reaction mixture was diluted with water (25 mL)
  4. extractionextracted with EtOAc (2×75 mL)
  5. dry with materialThe separated organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give crude
  9. customwhich was purified by neutral alumina column chromatography (EtOAc/Hexane 18:82)

Sources & evidence

ORD record
ord-2525f322c9e940c08c57e5664f2a9357
Source dataset
uspto-grants-2014_12
Patent number
US08916133B2

Reaction notes

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