Sodium Bicarbonate → Benzyl 4-((2-amino-4-(5-bromo-4-(2-ethoxy-2-oxoethyl)thiophene-2-carbonyl)phenyl)ethynyl)benzoate

HRID 1952491Notes

Reaction equation

HRID 1952491 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[C:16][C:17]3[CH:32]=[CH:31][C:20]([C:21]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:22])=[CH:19][CH:18]=3)=[C:11]([N+:33]([O-])=O)[CH:10]=2)=[O:8])=[CH:4][C:3]=1[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38].C([O-])(O)=O.[Na+]>CCOC(C)=O>[NH2:33][C:11]1[CH:10]=[C:9]([C:7]([C:5]2[S:6][C:2]([Br:1])=[C:3]([CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH:4]=2)=[O:8])[CH:14]=[CH:13][C:12]=1[C:15]#[C:16][C:17]1[CH:18]=[CH:19][C:20]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 67496549Benzyl 4-((4-(5-bromo-4-(2-ethoxy-2-oxoethyl)thiophene-2-carbonyl)-2-nitrophenyl)ethynyl)benzoate

Product 1

HCID 67496516Benzyl 4-((2-amino-4-(5-bromo-4-(2-ethoxy-2-oxoethyl)thiophene-2-carbonyl)phenyl)ethynyl)benzoateYield 105.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3 (450 mg, 0.71 mmol) in EtOAc (10 mL) was added stannous chloride dihydrate (642 mg, 2.84 mmol). The resulting mixture was refluxed for one hour under N2. The reaction mixture was then poured onto ice (5 g), and basified with a saturated NaHCO3 solution to pH 8. The white milky mixture was filtered through a Celite pad to remove tin oxides. The organic layer from the filtrate was dried over MgSO4, filtered, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/4:1) of the crude product gave the desired intermediate benzyl 4-((2-amino-4-(5-bromo-4-(2-ethoxy-2-oxoethyl)thiophene-2-carbonyl)phenyl)ethynyl)benzoate as a yellow foam (450 mg, 95%). 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J=8.0 Hz, 2H), 7.60 (d, J=8.0 Hz, 2H), 7.51-7.36 (m, 7H), 7.22-7.18 (m, 2H), 5.38 (s, 2H), 4.18 (q, J=7.2 Hz, 2H), 3.64 (s, 2H), and 1.27 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 186.72, 169.84, 166.01, 148.31, 143.21, 138.58, 136.12, 136.05, 135.39, 132.55, 131.71, 130.02, 129.98, 128.90, 128.62, 128.51, 127.71, 122.93, 118.70, 114.66, 111.47, 96.66, 88.41, 67.21, 61.63, 53.75, 35.32, and 14.44.

Workup

  1. temperatureThe resulting mixture was refluxed for one hour under N2
  2. additionThe reaction mixture was then poured onto ice (5 g)
  3. filtrationThe white milky mixture was filtered through a Celite pad
  4. customto remove tin oxides
  5. dry with materialThe organic layer from the filtrate was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customMPLC purification (Hex:EtOAc/4:1) of the crude product

Sources & evidence

ORD record
ord-89942e6883354db69b911720019b84c0
Source dataset
uspto-grants-2013_03
Patent number
US08404728B2

Reaction notes

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