Hydrochloric Acid → (S)-2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanol

HRID 2074414Notes

Reaction equation

HRID 2074414 reaction equation
B(F)(F)F.CCOCC.B(Cl)([C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1)[C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1.[CH:32]([O:35][C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:43][C:44]([C:46]1[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=1)=[O:45])([CH3:34])[CH3:33].Cl>C1COCC1.CO>[CH:32]([O:35][C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:43][C@@H:44]([C:46]1[CH:47]=[CH:48][N:49]=[CH:50][CH:51]=1)[OH:45])([CH3:34])[CH3:33]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6356Boron trifluorideHCID 11131038Chlorobis((1R,2S,3R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)boraneHCID 588701372-(2-Isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanone

Product 1

HCID 58870080(S)-2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen, at −30° C. slowly add BF3.□Et2O (1.7 g, 12 mmol) to a solution of (−)-B-chlorodiisopinocampheylborane (6.1 g, 19 mmol) in THF (40 mL). Cool the solution to −40° and add 2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanone (3.2 g, 12 mmol). Allow the solution to slowly come to room temperature and stir for 15 hr. Add MeOH and 3M aqueous HCl to the reaction mixture and stir for an additional 45 min. Evaporate the solvent and dissolve the residue in 3M aqueous HCl and wash with heptane. Neutralize the aqueous fraction with 50% aqueous NaOH to pH 12 and extract with EtOAc. Wash the organic phase was with brine and dry over MgSO4. Evaporate the solvent to afford a yellow oil. Purify the oil by chromatography over SiO2 using EtOAc:heptane (1:1). Evaporate the product-containing fraction to give (S)-2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanol as an oil, 1.16 g (36%); 1H-NMR (CDCl3) δ 8.5-6.8 (m, 7H), 4.9 (m, 1H), 4.3 (m, 1H), 3.1-2.9 (m, 2H), 2.3 (s, 3H), 1.3 (d, 6H).

Workup

  1. customat −30° C.
  2. temperatureCool the solution to −40°
  3. customto slowly come to room temperature
  4. customEvaporate the solvent
  5. dissolutiondissolve the residue in 3M aqueous HCl
  6. washwash with heptane
  7. extractionNeutralize the aqueous fraction with 50% aqueous NaOH to pH 12 and extract with EtOAc
  8. washWash the organic phase
  9. dry with materialdry over MgSO4
  10. customEvaporate the solvent
  11. customto afford a yellow oil
  12. customPurify the oil by chromatography over SiO2
  13. customEvaporate the product-containing fraction

Sources & evidence

ORD record
ord-0cbd786497e64a608787e95b6ea6c925
Source dataset
uspto-grants-2011_04
Patent number
US07919508B2

Reaction notes

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