Triethylamine → (3S)-3-{2-[(Methanesulfonyl)oxy]ethoxy}-4-(triphenylmethoxy)butyl methanesulfonate

HRID 977650Notes

Reaction equation

HRID 977650 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C@H:5]([CH2:9][O:10][C:11]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:6][CH2:7][OH:8].C(N(CC)CC)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>C(Cl)Cl>[CH3:37][S:38]([O:8][CH2:7][CH2:6][C@H:5]([O:4][CH2:3][CH2:2][O:1][S:38]([CH3:37])(=[O:40])=[O:39])[CH2:9][O:10][C:11]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)(=[O:40])=[O:39]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 10786707(S)-3-(2-hydroxyethoxy)-4-trityloxybutanol

Product 1

HCID 10209387(3S)-3-{2-[(Methanesulfonyl)oxy]ethoxy}-4-(triphenylmethoxy)butyl methanesulfonateYield 88.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(S)-3-(2-hydroxyethoxy)-4-(triphenylmethoxy)-1-butanol (500 g, 1.27 mole) was dissolved in 4.8 L of CH2Cl2, was cooled to 0° C. under N2, and triethylamine (386.4 g, 532 mL, 3.81 mole, 3.0 eq.) was added. Methanesulfonyl chloride (396.3 g, 268 mL, 3.46 mole, 2.7 eq.) was then added dropwise over 30 minutes at <5° C. The resultant reaction mixture was stirred at 0° to 5° C. for 1-2 hours and was monitored by HPLC. The reaction mixture was diluted with additional CH2Cl2 and was washed twice with 2 L of water and 2 L of an aqueous saturated solution of ammonium chloride. The aqueous layers were back-extracted with 1 L of CH2Cl2 and the combined organic layer was dried (MgSO4) and evaporated in vacuo to give a crude solid that was recrystallized from 1/1 heptane/ethyl acetate to give 615 g (88%) of (S)-3-[2-[(methylsulfonyl)oxy]ethoxy]-4-(triphenylmethoxy)-1-butanol methane sulfonate in three crops as a solid. NMR. MS.

Workup

  1. customThe resultant reaction mixture
  2. washwas washed twice with 2 L of water and 2 L of an aqueous saturated solution of ammonium chloride
  3. extractionThe aqueous layers were back-extracted with 1 L of CH2Cl2
  4. dry with materialthe combined organic layer was dried (MgSO4)
  5. customevaporated in vacuo
  6. customto give a crude solid that
  7. customwas recrystallized from 1/1 heptane/ethyl acetate

Sources & evidence

ORD record
ord-a15cc2cbc4ba45b4a553081091b46edd
Source dataset
uspto-grants-1997_03
Patent number
US05614647

Reaction notes

Loading…