Tetrahydrofuran → 5-(2-Bromoacetyl)-4-(2,4-dichlorophenyl)-2-morpholinothiophene-3-carbonitrile

HRID 2091690Notes

Reaction equation

HRID 2091690 reaction equation
[Br:1][CH:2](Br)[C:3]([C:5]1[S:9][C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[C:7]([C:16]#[N:17])[C:6]=1[C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[Cl:25])=[O:4].C1COCC1.P([O-])(OCC)OCC>>[Br:1][CH2:2][C:3]([C:5]1[S:9][C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[C:7]([C:16]#[N:17])[C:6]=1[C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[Cl:25])=[O:4]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 3780918DiethylphosphiteHCID 86640158HCID 86640158, compound

Product 1

HCID 866401575-(2-Bromoacetyl)-4-(2,4-dichlorophenyl)-2-morpholinothiophene-3-carbonitrileYield 30%

Procedure

To a mixture of 5-(dibromoacetyl)-4-(2,4-dichlorophenyl)-2-morpholin-4-ylthiophene-3-carbonitrile (46.9 mg, 0.0000870 mol) in THF (0.78 mL, 0.0096 mol) was added diethyl phosphite (13.7 uL, 0.000107 mol) and TEA (14.9 uL, 0.000107 mol) at 0° C. After addition, the mixture was warmed to rt after 20 min. The reaction mixture was evaporated and the residue was suspended in ice/water. The solid was filtered and purified by column chromatography to afford 5-(2-bromoacetyl)-4-(2,4-dichlorophenyl)-2-morpholinothiophene-3-carbonitrile (12 mg, 30%). LCMS: (FA) ES+ 460.88; 1H NMR (400 MHz, d1-chloroform) δ: 7.59 (d, 1H), 7.42 (dd, 1H), 7.33 (d, 1H), 3.90-3.85 (m, 4H), 3.75-3.69 (m, 5H), 3.62 (d, 1H).

Workup

  1. additionAfter addition
  2. customThe reaction mixture was evaporated
  3. filtrationThe solid was filtered
  4. custompurified by column chromatography

Sources & evidence

ORD record
ord-cc3c153feaf44b2e88bcde48695763f6
Source dataset
uspto-grants-2013_05
Patent number
US08440664B2

Reaction notes

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