1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone → (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol

HRID 2273846Notes

Reaction equation

HRID 2273846 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:12](=[O:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]>C(#N)C.CC1C=CC(C(C)C)=CC=1.CC1C=CC(S([N-][C@H]([C@@H](N)C2C=CC=CC=2)C2C=CC=CC=2)(=O)=O)=CC=1.Cl[Ru+]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@@H:12]([OH:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]

Participants

4

Reactant 1

HCID 717245451-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone

Product 1

HCID 86693820(R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanolYield 87%

Reagents, catalysts & solvents 2

HCID 11974997Chloridoruthenium(1+) [(1S,2S)-2-amino-1,2-diphenylethyl](4-methylbenzene-1-sulfonyl)azanide--1-methyl-4-(propan-2-yl)benzene (1/1/1)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
22.5 °C

Procedure

A mixture of 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone (1.2 g, 4.4 mmol), RuCl(p-cymene)[(S,S)-Ts-DPEN] (28 mg, 0.044 mmol), and 5:2 formic acid-triethylamine complex (2.2 mL) in acetonitrile (7.2 mL) was stirred at 20-25° C. for 40 h. The mixture was evaporated to dryness and the residue was chromatographed on a silica gel column, using a hexanes-ethyl acetate gradient. The appropriate fractions were pooled and evaporated. The residue was triturated with heptane (25 mL) and the resulting slurry was filtered and dried under vacuum to provide (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol as a white solid (1.05 g, 87% yield); achiral HPLC (Hypersil BDS C8, 5.0 μm, 250×4.6 mm, 1.5 mL/min, 278 nm, 90/10 gradient to 80/20 0.1% aqueous TFA/MeOH over 10 min then gradient to 10/90 0.1% aqueous TFA/MeOH over the next 15 min): 12.37 (99.8%); chiral HPLC (Chiralpak AD-H 5.0 μm Daicel, 250×4.6 mm, 1.0 mL/min, 280 nm, 85:15 heptane-i-PrOH): 18.07 (0.51%), 20.43 (99.4%); 1H NMR(CHCl3-d) δ 1.48 (t, J=7.0 Hz, 3H), 2.77 (dd, J=1.1, 2.6 Hz, 1H), 3.05 (s, 3H), 3.17 (dd, J=0.9, 14.7 Hz, 1H), 3.46 (dd, J=10.1, 14.6 Hz, 1H), 3.88 (s, 3H), 4.11 (q, J=7.0 Hz, 2H), 5.27-5.32 (m, 1H), 6.82-6.95 (m, 3H).

Workup

  1. customThe mixture was evaporated to dryness
  2. customthe residue was chromatographed on a silica gel column
  3. customevaporated
  4. customThe residue was triturated with heptane (25 mL)
  5. filtrationthe resulting slurry was filtered
  6. customdried under vacuum

Sources & evidence

ORD record
ord-2c572d3fe04d472a9099dce9c473d11b
Source dataset
uspto-grants-2015_09
Patent number
US09126906B2

Reaction notes

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