Sodium Iodide → HCID 66759489, compound

HRID 389544

Reaction equation

HRID 389544 reaction equation
[H-].[Na+].C(O[CH:6]([O:10][CH2:11][CH3:12])[C:7]([NH2:9])=[O:8])C.[Br:13][C:14]1[C:18]([CH2:19]Br)=[CH:17][S:16][CH:15]=1.[I-].[Na+].C1[CH2:27][O:26][CH2:25]C1>>[Br:13][C:14]1[C:18]([CH2:19][NH:9][C:7](=[O:8])[CH:6]([O:10][CH2:11][CH3:12])[CH2:25][O:26][CH3:27])=[CH:17][S:16][CH:15]=1

Participants

6

Reactant 5

HCID 5238Sodium IodideHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 1007652,2-DiethoxyacetamideHCID 133547593-Bromo-4-(bromomethyl)thiophene

Product 1

HCID 66759489HCID 66759489, compoundYield 35%

Procedure

To a suspension of sodium hydride (162 mg, 6.74 mmol) in THF (14 mL, 170 mmol) was added 2,2-diethoxyacetamide (949 mg, 6.45 mmol) in portions, followed by 3-bromo-4-(bromomethyl)thiophene (1.50 g, 5.86 mmol) dropwise as a solution in THF (3 mL) and sodium iodide (87.8 mg, 0.586 mmol). The reaction mixture was heated to reflux for 18 h and then concentrated. The residue was then partitioned between water (40 mL) and ethyl acetate (40 mL). The layers were separated and the aqueous layer was further extracted with ethyl acetate (2×30 mL). The combined organic fractions were dried over sodium sulfate, filtered, and concentrated. Purification by ISCO chromatography (5 to 30% ethyl acetate:heptane) afforded 729 mg (35%) of the title compound as a clear, colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.26-7.29 (m, 1 H), 7.23-7.25 (m, 1 H), 6.99 (br. s., 1 H), 4.83 (s, 1 H), 4.44 (dd, J=6.1, 0.8 Hz, 2 H), 3.21-3.98 (m, 4 H), 1.25 (t, J=6.9 Hz, 6 H); MS (ESI): 322.17, 324.15 [M+H]+; HPLC tR=3.26 min (ZQ3, polar—4 min).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated
  4. customThe residue was then partitioned between water (40 mL) and ethyl acetate (40 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was further extracted with ethyl acetate (2×30 mL)
  7. dry with materialThe combined organic fractions were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by ISCO chromatography (5 to 30% ethyl acetate:heptane)

Sources & evidence

ORD record
ord-7273c1aef4604380aa8663eaf10690f6
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Linked notes

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