2-Chloro-1-(6-(2,5-dimethyl-1H-pyrrol-1-YL)pyridin-3-YL)ethanone → (1R)-2-Chloro-1-[6-(2.5-dimethyl-pyrrol-1-yl)-pyridin-3-yl]-ethanol

HRID 1004655Notes

Reaction equation

HRID 1004655 reaction equation
B1([C@H]2[C@H](C)[C@@H]3C(C)(C)[C@H](C3)C2)C2CCCC1CCC2.[Cl:20][CH2:21][C:22]([C:24]1[CH:25]=[N:26][C:27]([N:30]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]2[CH3:36])=[CH:28][CH:29]=1)=[O:23]>>[Cl:20][CH2:21][C@@H:22]([C:24]1[CH:25]=[N:26][C:27]([N:30]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]2[CH3:36])=[CH:28][CH:29]=1)[OH:23]

Participants

3

Reactant 2

HCID 113796602-Chloro-1-(6-(2,5-dimethyl-1H-pyrrol-1-YL)pyridin-3-YL)ethanoneHCID 100979710(R)-Alpine borane

Product 1

HCID 11379719(1R)-2-Chloro-1-[6-(2.5-dimethyl-pyrrol-1-yl)-pyridin-3-yl]-ethanolYield 37.3%

Conditions

Temperature
0 °C

Procedure

(R)-Alpine borane (1.5 L, 0.5 M in tetrahydrofuran) was added slowly to a cooled (0° C.), neat, 2-chloro-1-[6-(2,5-dimethyl-pyrrol-1-yl)-pyridin-3-yl]-ethanone (Example 140; 93 g). The mixture was warmed to room temperature and reduced to one third its original volume by distilling tetrahydrofuran. After four days, the mixture was cooled to 0° C. and 3 M aqueous solution of K2CO3 (600 mL) was added. Then the reaction mixture was oxidized by drop wise addition of 30% H2O2 (250 mL). After stirring at room temperature for 3 h, the reaction mixture was diluted ethyl acetate, organic layer was separated. Aqueous portion was extracted (ethyl acetate), combined organic extracts were washed with water and dried. After concentration in vacuo, the resulting oil was purified by chromatography on silica gel (hexanes/ethyl acetate as eluent) to afford a yellow solid (35 g). 1H NMR (CDCl3, 300 MHz) δ 8.59 (m, 1 H), 7.88 (dd, 8.1 Hz, 2.2 Hz, 1 H), 7.26 (m, 1 H), 5.91 (m, 2 H), 4.96 (m, 1 H), 3.78 (m, 2 H), 3.35 (br s, 1 H), 2.11 (2, 6 H); MS (FAB) m/z 251 (MH+); Anal. calcd for C13H15N2OCl: C, 62.28; H, 6.03; N, 11.17. Found: C, 61.95; H, 6.03; N, 10.92; Rf =0.4 (60:40 hexanes/ethyl acetate).

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. distillationby distilling tetrahydrofuran
  3. temperaturethe mixture was cooled to 0° C.
  4. addition3 M aqueous solution of K2CO3 (600 mL) was added
  5. additionThen the reaction mixture was oxidized by drop wise addition of 30% H2O2 (250 mL)
  6. customwas separated
  7. extractionAqueous portion was extracted (ethyl acetate)
  8. washwere washed with water
  9. customdried
  10. concentrationAfter concentration in vacuo
  11. customthe resulting oil was purified by chromatography on silica gel (hexanes/ethyl acetate as eluent)

Sources & evidence

ORD record
ord-7027f387731b4b4caf9b24679cb61afb
Source dataset
uspto-grants-2000_04
Patent number
US06051586

Reaction notes

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