Ethyl chloroformate → HCID 72192937, compound

HRID 1404835Notes

Reaction equation

HRID 1404835 reaction equation
[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[CH:6][C:5]([NH2:17])=[C:4]([N+:18]([O-])=O)[CH:3]=1.[Cl-].[NH4+].CCN(C(C)C)C(C)C.Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34]>CO.[Zn]>[NH2:17][C:5]1[CH:6]=[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[C:2]([F:1])=[CH:3][C:4]=1[NH:18][C:33](=[O:34])[O:35][CH2:36][CH3:37]

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 86700478HCID 86700478, compound

Product 1

HCID 72192937HCID 72192937, compoundYield 22.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of compound 3 (0.400 g, 1.40 mmol, 1.00 equiv) in methanol (10 mL) was added zinc powder (0.470 g, 7.10 mmol, 5.00 equiv) followed by ammonium chloride solution (0.380 g, 9.10 mmol, 5.00 equiv) drop wise. After being stirred for 5 h at RT, DIPEA (0.155 g, 1.54 mmol, 1.10 equiv) and ethyl chloroformate (0.151 g, 1.40 mmol, 1.00 equiv) were added to reaction mixture at 0° 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 (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 silica gel column chromatography (EtOAc/Hexane 1:4) to afford to compound 3A (0.100 g, 21.0%) as brown solid. TLC: 40% EtOAc/Hexane (Rf: 0.50); 1HNMR (400 MHz, DMSO-d6): δ 8.27 (br s, 1H), 7.39-7.34 (m, 2H), 7.12 (t, J=8.8 Hz, 2H), 6.81-6.78 (m, 1H), 5.93 (d, J=9.2 Hz, 1H), 5.79 (t, J=6.4 Hz, 1H), 4.42 (s, 2H), 4.22 (d, J=6.0 Hz, 2H), 4.03 (q, J=6.8 Hz, 2H), 1.19 (t, J=6.8 Hz, 3H); LC-MS: m/z=322 (M++1) at RT 3.54 (95.8% purity); UPLC purity: 98.8%

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 (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 silica gel column chromatography (EtOAc/Hexane 1:4)

Sources & evidence

ORD record
ord-ab598ec0935d47108fd69ba1d9346ca8
Source dataset
uspto-grants-2014_12
Patent number
US08916133B2

Reaction notes

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