Hydrochloric Acid → (2RS,3SR)-3-(2-Ethoxyphenoxy)-2-mesyloxy-3-phenyl-1-propanol

HRID 843378Notes

Reaction equation

HRID 843378 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[Si](Cl)(C)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29].Cl>C(OCC)(=O)C.C(N(CC)CC)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]([O:11][S:28]([CH3:27])(=[O:30])=[O:29])[CH2:9][OH:10])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 31297Methanesulfonyl chlorideHCID 13479304(2RS,3RS)-3-(2-Ethoxyphenoxy)-1,2-dihydroxy-3-phenylpropane

Product 1

HCID 73084453(2RS,3SR)-3-(2-Ethoxyphenoxy)-2-mesyloxy-3-phenyl-1-propanolYield 102.9%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
-17 °C

Procedure

3-(2-Ethoxyphenoxy)-2-hydroxy-3-phenylpropanol from Example 2 (0.288 g, 1 mmole) and triethylamine ((0.15 mL, 1.1 mmole) were dissolved in ethyl acetate (5 mL) and cooled to −17° C. Trimethylsilyl chloride (0.13 mL, 1.0 mmole) dissolved in ethyl acetate (2 mL) 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. Triethylamine (0.15 mL, 1.1 mmole) was added, followed by methanesulfonyl chloride (0.085 mL, 1.1 mmole) dissolved ethyl acetate (2 mL) keeping the temperature below −15° C. The mixture was stirred below −15° C. for 15 minutes. Hydrochloric acid (2N, 2 mL) was added and the mixture was allowed to warm to 20-25° C. and stirred for 30 minutes. The phases were separated and the organic phase was washed with saturated aqueous sodium chloride solution (5 mL) and dried over sodium sulfate. The solution was evaporated to yield 0.377 g of an oil. The oil was chromatographed on silica (230-400 mesh) eluting with 1:1 hexane-ethyl acetate. The product-containing fractions were concentrated to yield 0.33 g (91%) of the title compound as an oil that solidified on standing; mp 83-86° C.; 1H NMR (400.13 MHZ, CDCl3) d 1.66 (t, J=8.2 Hz, 3H), 2.85 (s, 3H), 4.14-4.35 (m, 4H), 5,12 (m, 1H), 5.52 (d, J=6.1 Hz), 6.8-7.15 (m, 4H), 7.5-7.7 (m, 5H); 13C NMR (100.62 MHZ, CDCl3) d 14.73, 37.80, 62.19, 64.27, 81.40, 84.04, 112.88, 117.19, 120.67, 122.86, 127.40, 128.77, 128.86, 137.02, 146.40, 149.30; MS (ei ) m/e 366.

Workup

  1. additionwas added over 10 minutes
  2. customthe temperature below −15° C.
  3. customformed during this addition
  4. customthe temperature below −15° C
  5. stirringThe mixture was stirred below −15° C. for 15 minutes
  6. temperatureto warm to 20-25° C.
  7. stirringstirred for 30 minutes
  8. customThe phases were separated
  9. washthe organic phase was washed with saturated aqueous sodium chloride solution (5 mL)
  10. dry with materialdried over sodium sulfate
  11. customThe solution was evaporated

Sources & evidence

ORD record
ord-d656d570293e45c196a989092bf9f0c2
Source dataset
uspto-grants-2002_04
Patent number
US06376711B1

Reaction notes

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