ethyl 6-chloro-5-azido-2-(trifluoromethyl)-2H-chromene-3-carboxylate → ethyl 6-chloro-5-amino-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855146Notes

Reaction equation

HRID 855146 reaction equation
[Cl:1][C:2]1[C:3]([N:21]=[N+]=[N-])=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2>CO>[Cl:1][C:2]1[C:3]([NH2:21])=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:13])[F:14])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2

Participants

3

Reactant 1

HCID 58934903ethyl 6-chloro-5-azido-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 58934551ethyl 6-chloro-5-amino-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 61.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the suspension of stannous chloride hydrate (5.5 g, 24.1 mmol) in 150 mL of methanol was added at room temperature ethyl 6-chloro-5-azido-2-(trifluoromethyl)-2H-chromene-3-carboxylate (5.6 g, 16.1 mmol) in one portion. The reaction mixture gradually turned yellowish. After stirred at room temperature for about 45 min, the reaction turned a clear yellow solution. The volatiles were then removed. The residue was dissolved in EtOAc, and the resulting organic solution was washed with 5% sodium hydroxide solution (×4), brine, and dried over anhydrous magnesium sulfate. After removing the solvents, the residue was purified on silica gel column with 3:7 EtOAc/hexane, it gave 3.2 g of yellow solid. A small fraction of the product was further purified on reverse phase HPLC, it provided a yellow solid. LC-MS(ES+) 322.2(M+1, 100). 1H NMR (CDCl3/400 MHz) 7.80(s, 1H), 7.16(d, J=8.8 Hz, 1H), 6.35(d, J=8.8 Hz, 1H), 5.65(q, J=7.2 Hz, 1H), 4.31(m, 2H), 1.34(t, J=7.2 Hz, 3H). 19F NMR(CDCl3/400 MHz) −78.55(d, J=7.4 Hz). 13C NMR(CDCl3/300 Mhz) 164.1, 152.8, 141.3, 133.1, 131.7, 123.7(q, J=287.7 Hz), 115.2, 113.4, 107.2, 106.6, 70.3(q, J=33.2 Hz), 61.7, 14.5. MS(ES+) 322.1(M+1, 75%), HRMS(EI+) m/z calc for (C13H11ClF3NO3): 321.0380 (M+), found, 321.0359(M+).

Workup

  1. customThe volatiles were then removed
  2. dissolutionThe residue was dissolved in EtOAc
  3. washthe resulting organic solution was washed with 5% sodium hydroxide solution (×4), brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customAfter removing the solvents
  6. customthe residue was purified on silica gel column with 3:7 EtOAc/hexane, it

Sources & evidence

ORD record
ord-3d4db05140e9401c8e31544b302502d8
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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