Phosphorus oxychloride → Methyl 3-(4-chloro-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidin-2-yl)propionate

HRID 1056841Notes

Reaction equation

HRID 1056841 reaction equation
[CH3:1][O:2][C:3](=[O:20])[CH2:4][CH2:5][C:6]1[N:7]=[C:8](O)[C:9]2[C:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C:13]=3[S:12][C:10]=2[N:11]=1.O=P(Cl)(Cl)[Cl:23]>>[CH3:1][O:2][C:3](=[O:20])[CH2:4][CH2:5][C:6]1[N:7]=[C:8]([Cl:23])[C:9]2[C:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C:13]=3[S:12][C:10]=2[N:11]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178500074HCID 178500074, compound

Product 1

HCID 11001423Methyl 3-(4-chloro-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidin-2-yl)propionateYield 47%

Procedure

A solution of 3-(4-hydroxy-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl)-propionic acid methyl ester (2 g, 0.0068 mol) in POCl3 (10 ml) was refluxed for 2 hrs. After consumption of starting material, excess of POCl3 was distilled off. The reaction mixture was quenched with ice and extracted with ethyl acetate (3×25 ml). The combined organic layers were dried over Na2SO4, concentrated and purified by chromatography on 60-120 silica using ethyl acetate (30%) in hexane as eluant to give 1 g (47%) of 3-(4-chloro-5,6,7,8-tetrahydro-[1]benzothiopheno[2,3-d]pyrimidin-2-yl)-propionic acid methyl ester. 1H NMR (400 MHz, DMSO) δ ppm=1.83 (m, 4H), 2.8 (m, 4H), 2.98 (m, 2H), 3.2 (t, 2H), 3.57 (s, 3H). LC-MS: [M+H]=311.1.

Workup

  1. customAfter consumption of starting material
  2. distillationexcess of POCl3 was distilled off
  3. customThe reaction mixture was quenched with ice
  4. extractionextracted with ethyl acetate (3×25 ml)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by chromatography on 60-120 silica

Sources & evidence

ORD record
ord-b33551b136f24830a2ded7de1f1df817
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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