Sodium Formate → (R)-1-(7-Bromoquinolin-2-yl)ethanol

HRID 2176213Notes

Reaction equation

HRID 2176213 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12](=[O:14])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.C([O-])=O.[Na+]>O.O1CCCC1.CC1C=CC(C(C)C)=CC=1.CC1C=CC(C(C)C)=CC=1.Cl[Ru]Cl.Cl[Ru]Cl.CC1C=CC(S(N[C@@H]([C@H](N)C2C=CC=CC=2)C2C=CC=CC=2)(=O)=O)=CC=1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([OH:14])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 2723810Sodium FormateHCID 867060471-(7-Bromoquinolin-2-yl)ethanone

Product 1

HCID 86706048(R)-1-(7-Bromoquinolin-2-yl)ethanolYield 98.4%

Reagents, catalysts & solvents 4

HCID 2734565N-((1R,2R)-2-Amino-1,2-diphenylethyl)-4-methylbenzene-1-sulfonamideCatalystHCID 10908223Dichloro(p-cymene)ruthenium(II) dimerCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Dichloro (p-cymene) ruthenium(II) dimer (61 mg, 0.100 mmol) and (1R,2R)-(−)—N-p-tosyl-1,2-diphenylethylenediamine (88 mg, 0.012 mmol) was suspended in degassed water (40 mL) and the mixture was degassed with nitrogen for 5 min. The mixture was stirred at 70° C. under nitrogen for 90 min. The resulting turbid orange mixture was allowed to cool to room temperature. 1-(7-Bromo-quinolin-2-yl)-ethanone (5.00 g, 20 mmol) in degassed tetrahydrofuran (40 mL) was added followed by sodium formate (6.8 g, 100 mmol) and the reaction mixture was degassed with nitrogen for 5 min. The reaction mixture was vigorously stirred at 40° C. for 4 h and allowed to cool. It was then diluted with ethyl acetate and water and the organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of 0% to 30% ethyl acetate in iso-hexanes to afford the title compound (4.96 g, 98%) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 1.59 (d, J=6.7 Hz, 3H), 4.85 (d, J=4.5 Hz, 1H), 5.04-5.07 (m, 1H), 7.40 (d, J=8.5 Hz, 1H), 7.64 (dd, J=8.7, 1.6 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 8.15 (d, J=8.5 Hz, 1H), 8.28 (d, J=1.6 Hz, 1H). LCMS (m/z) 252.1/254.1 [M+H], Tr=1.74 min.

Workup

  1. customthe mixture was degassed with nitrogen for 5 min
  2. temperatureto cool to room temperature
  3. customthe reaction mixture was degassed with nitrogen for 5 min
  4. stirringThe reaction mixture was vigorously stirred at 40° C. for 4 h
  5. temperatureto cool
  6. additionIt was then diluted with ethyl acetate and water
  7. customthe organic layer was separated
  8. washwashed with water and brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-2c7cb462ff4b4e0bba6c4af3a171079a
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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