Tetrahydrofuran → 7-Chloro-2,3-dihydro-5-(1-hydroxyethyl)-3-methyl-furo[2,3-c]pyridine

HRID 1637774Notes

Reaction equation

HRID 1637774 reaction equation
[Cl:1][C:2]1[C:7](CC=C)=[C:6](I)[CH:5]=[C:4]([CH:12]([OH:14])[CH3:13])[N:3]=1.[PH2](O)=O.C(N(CC)CC)C.[CH2:25]1C[O:28][CH2:27][CH2:26]1>>[Cl:1][C:2]1[N:3]=[C:4]([CH:12]([OH:14])[CH3:13])[CH:5]=[C:6]2[CH:26]([CH3:25])[CH2:27][O:28][C:7]=12

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 4124402Phosphinic AcidHCID 187998202-Chloro-3-(1-propen-3-yl)-4-iodo-6-(1-hydroxyethyl)-pyridine

Product 1

HCID 108224987-Chloro-2,3-dihydro-5-(1-hydroxyethyl)-3-methyl-furo[2,3-c]pyridineYield 97%

Procedure

A solution of 2-chloro-3-(1-propen-3-yl)-4-iodo-6-(1-hydroxyethyl)-pyridine (1.06 g, 3.14 mmol) in THF (5 mL) is treated with 50% hypophosphorous acid (2.13 g, 15.73 mmol), triethylamine (1.75 g, 17.33 mmol), and 2,2'-azobis(2-methylpropino-nitrile) (AIBN; 192 mg, 1.23 mmol). The solution is stirred at reflux for 2 hours. The solution is allowed to cool and concentrated in vacuo. Sat'd NaHCO3 is added, and the mixture is extracted 3× EtOAc. The organics are dried over MgSO4, and concentrated in vacuo. The crude light yellow oil is chromatographed (SiO2, hexane/ethyl acetate, 2:1) to yield 650 mg (97%) of 7-chloro-2,3-dihydro-5-(1-hydroxyethyl)-3-methyl-furo[2,3-c]pyridine, mp 67-68° C.

Workup

  1. temperatureat reflux for 2 hours
  2. temperatureto cool
  3. concentrationconcentrated in vacuo
  4. additionSat'd NaHCO3 is added
  5. extractionthe mixture is extracted 3× EtOAc
  6. dry with materialThe organics are dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude light yellow oil is chromatographed (SiO2, hexane/ethyl acetate, 2:1)

Sources & evidence

ORD record
ord-ce3ddfe45fa4441ca95e8fd52beb403c
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

Loading…