Chlorotrimethylsilane → (2RS,3SR)-3-(2-Ethoxyphenoxy)-2-hydroxy-3-phenyl-1-(trimethylsilyloxy)propane

HRID 843376Notes

Reaction equation

HRID 843376 reaction equation
[CH2:1]([O:3][C:4]1[CH:21]=[CH:20][CH:19]=[CH:18][C:5]=1[O:6][CH:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:8]([OH:11])[CH2:9][OH:10])[CH3:2].C(N(CC)CC)C.[CH3:29][Si:30](Cl)([CH3:32])[CH3:31].CCCCC>C(OCC)(=O)C>[CH2:1]([O:3][C:4]1[CH:21]=[CH:20][CH:19]=[CH:18][C:5]=1[O:6][CH:7]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH:8]([OH:11])[CH2:9][O:10][Si:30]([CH3:32])([CH3:31])[CH3:29])[CH3:2]

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8003PentaneHCID 8471TriethylamineHCID 13479304(2RS,3RS)-3-(2-Ethoxyphenoxy)-1,2-dihydroxy-3-phenylpropane

Product 1

HCID 9841838(2RS,3SR)-3-(2-Ethoxyphenoxy)-2-hydroxy-3-phenyl-1-(trimethylsilyloxy)propaneYield 99.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-17 °C

Procedure

3-(2-Ethoxyphenoxy)-2-hydroxy-3-phenylpropanol from Example 2 (1.44 g, 5 mmole) and triethylamine ((0.77 mL, 5.5 mmole) were dissolved in ethyl acetate (15 ml) and cooled to −17° C. Trimethylsilyl chloride (0.64 mL, 5.0 mmole) dissolved in 5 mL of ethyl acetate was added over 10 minutes keeping the temperature below −15° C. a white precipitate formed during this addition. The mixture was stirred below −15° C. for 15 minutes, and 20 mL of pentane was added. The solids were removed by filtration and the filtrate was concentrated under vacuum to a cloudy oil. The oil was chromatographed on silica (230-400 mesh) eluting with 4:1 heptane-ethyl acetate. The product-containing fractions were concentrated to yield 1.80 g (88.5%) of the title compound as a clear colorless oil; 1H NMR (400.13 MHZ, CDCl3) d 0.09 (s, 9H), 1.47 (t, J=6.8 Hz, 3H), 2.82 (d, J=5.2, 1H), 3.80 (m, 3H), 4.0-4.11 (m, 4H), 5.08 (d, J=6.0, 1H), 6.76 (m, 2H), 6.85 (m, 2H), 7.2-7.45 (m, 5H); 13C NMR (100.62 MHZ, CDCl3) d 0.0, 15.54, 63.34, 65.06, 75.22, 83.71, 114.28, 118.60, 121.51, 122.95, 127.84, 128.49, 128.84, 138.93, 148.34, 150.40; MS (ei) m/e 360.

Workup

  1. additionwas added over 10 minutes
  2. customthe temperature below −15° C.
  3. customformed during this addition
  4. customThe solids were removed by filtration
  5. concentrationthe filtrate was concentrated under vacuum to a cloudy oil
  6. customThe oil was chromatographed on silica (230-400 mesh)
  7. washeluting with 4:1 heptane-ethyl acetate
  8. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-7333217735e846719bca401e0d42f10d
Source dataset
uspto-grants-2002_04
Patent number
US06376711B1

Reaction notes

Loading…