Boron trifluoride etherate → 2-(1-Chloro-3-methylnaphthalen-2-yl)-2-(1,1,1-trifluoro-2-methylpropan-2-yloxy)ethanol

HRID 926216Notes

Reaction equation

HRID 926216 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH3:12])[C:3]=1[C@@H:13]1[CH2:15][O:14]1.[F:16][C:17]([F:23])([F:22])[C:18]([OH:21])([CH3:20])[CH3:19].B(F)(F)F.CCOCC>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH3:12])[C:3]=1[CH:13]([O:21][C:18]([CH3:20])([CH3:19])[C:17]([F:23])([F:22])[F:16])[CH2:15][OH:14]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 681821,1,1-Trifluoro-2-methylpropan-2-olHCID 89676658(R)-2-(1-chloro-3-methylnaphthalen-2-yl)oxirane

Product 1

HCID 896766802-(1-Chloro-3-methylnaphthalen-2-yl)-2-(1,1,1-trifluoro-2-methylpropan-2-yloxy)ethanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (R)-2-(1-chloro-3-methylnaphthalen-2-yl)oxirane (340 mg, 1.56 mmol) and 2-trifluoromethyl-2-propanol (4.3 mL, 38.97 mmol) in CH2Cl2 (4.3 mL), boron trifluoride diethyl etherate (1.9 mL, 15.60 mmol) was added at 0° C. The reaction mixture was stirred for 16 h at 0° C. and allowed to warm to room temperature overnight. The mixture was quenched with saturated aqueous NaHCO3, and then diluted with CH2Cl2. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated and purified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes) to give 2-(1-chloro-3-methylnaphthalen-2-yl)-2-(1,1,1-trifluoro-2-methylpropan-2-yloxy)ethanol. 1H-NMR: 400 MHz, (CDCl3) δ 8.27 (d, J=8.4 Hz, 1H), 7.73 (d, J=7.6 Hz, 1H), 7.57-7.49 (m, 3H), 5.90 (dd, J=9.6, 4.4 Hz, 1H), 3.98 (t, J=11.2 Hz, 1H), 3.66 (dd, J=12.0, 4.0 Hz, 1H), 2.69 (s, 3H), 2.18 (br s, 1H), 1.45 (s, 3H), 1.19 (s, 3H).

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe mixture was quenched with saturated aqueous NaHCO3
  3. additiondiluted with CH2Cl2
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9a6a2e6749bd4e8e80e6786dc0e216cb
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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