Methanesulfonic Acid → HCID 66704603, compound

HRID 425081Notes

Reaction equation

HRID 425081 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:24])=[C:6]([CH:23]=1)[CH2:7][C:8]1[CH:22]=[CH:21][C:11]([O:12][CH2:13][CH2:14][O:15][C@H:16]2[CH2:20][CH2:19][O:18][CH2:17]2)=[CH:10][CH:9]=1.[CH2:25]([Li])CCC.C[Si](C)(C)[O:32][C@@H:33]1[C@@H:38]([O:39][Si](C)(C)C)[C@H:37]([O:44][Si](C)(C)C)[C@@H:36]([CH2:49][O:50][Si](C)(C)C)[O:35][C:34]1=[O:55].CS(O)(=O)=O>C1(C)C=CC=CC=1.O1CCCC1.C1(C)C=CC=CC=1.CO>[Cl:24][C:5]1[CH:4]=[CH:3][C:2]([C:34]2([O:55][CH3:25])[C@H:33]([OH:32])[C@@H:38]([OH:39])[C@H:37]([OH:44])[C@@H:36]([CH2:49][OH:50])[O:35]2)=[CH:23][C:6]=1[CH2:7][C:8]1[CH:22]=[CH:21][C:11]([O:12][CH2:13][CH2:14][O:15][C@H:16]2[CH2:20][CH2:19][O:18][CH2:17]2)=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 6395Methanesulfonic AcidHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 66704611(S)-3-(2-(4-(5-bromo-2-chlorobenzyl)phenoxy)ethoxy)tetrahydrofuranHCID 178418339Butyllithium

Product 1

HCID 66704603HCID 66704603, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-65 °C

Procedure

To a −65° C. solution of (S)-3-(2-(4-(5-bromo-2-chlorobenzyl)phenoxy)ethoxy)tetrahydrofuran (200 mg, 0.49 mmol) in anhydrous toluene/tetrahydrofuran (6 mL, v/v=2:1) was added dropwise n-butyllithum (2.5 M in hexane, 0.3 mL), and the pale yellow mixture was stirred for 30 min at −65° C. The mixture was transferred to a −65° C. solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one (280 mg, 0.73 mmol) in toluene (4 mL). The mixture was stirred at −65° C. for 2 h until starting material was consumed. The reaction was quenched with methanesulfonic acid (0.04 mL, 1.7 mmol) in methanol (6 mL), and the mixture was allowed to warm to 20° C. and stirred overnight. The reaction was quenched with saturated sodium bicarbonate. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with saturated sodium bicarbonate, then with water and then with brine prior to drying over anhydrous sodium sulfate. Removal of volatiles afforded 200 mg of crude solid product, which was used in the next step without further purification.

Workup

  1. customwas transferred to a −65° C.
  2. stirringThe mixture was stirred at −65° C. for 2 h
  3. customwas consumed
  4. temperatureto warm to 20° C.
  5. stirringstirred overnight
  6. customThe reaction was quenched with saturated sodium bicarbonate
  7. customThe organic phase was separated
  8. extractionthe aqueous phase was extracted with ethyl acetate
  9. washwashed with saturated sodium bicarbonate
  10. dry with materialwith water and then with brine prior to drying over anhydrous sodium sulfate
  11. customRemoval of volatiles

Sources & evidence

ORD record
ord-ecc9a36285544a398ac430e3464dee3a
Source dataset
uspto-grants-2012_01
Patent number
US08106021B2

Reaction notes

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