Triethylamine → (R)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl methanesulfonate

HRID 1735874Notes

Reaction equation

HRID 1735874 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][C@@H:6]([OH:13])[CH2:7]2.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(OCC)C>[CH3:21][S:22]([O:13][C@@H:6]1[CH2:5][CH2:4][C:3]2[C:8](=[CH:9][C:10]([F:12])=[CH:11][C:2]=2[F:1])[CH2:7]1)(=[O:24])=[O:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 54483016(2R)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ol

Product 1

HCID 53750897(R)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl methanesulfonateYield 103.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A mixture of (R)-5,7-difluoro-1,2,3,4-tetrahydro-2-hydroxynaphthalene (59.0 g, 0.32 mol), prepared as in Example 3, and triethylamine (13.8 M, 74.2 mL, 0.53 mol) in 1.78 L of diethyl ether was cooled using a methanol/ice bath. Methanesulfonyl chloride (12.9 M, 37.2 mL, 0.48 mol) was added under argon over 5-10 minutes and the mixture was stirred at room temperature for 18 hours. The mixture was partitioned between water and ether and the ether layer was separated and the aqueous layer was extracted with ether. The combined ether layers were washed once with each of 1N hydrochloric acid, saturated sodium bicarbonate solution and brine and then dried over magnesium sulfate. Evaporation gave crude (R)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl methanesulfonate as an off-white solid (87.12 g), m.p. 79°-80° C. [α]D25 =+16.77° (c=2.0, CHCl3).

Workup

  1. temperaturewas cooled
  2. customThe mixture was partitioned between water and ether
  3. customthe ether layer was separated
  4. extractionthe aqueous layer was extracted with ether
  5. washThe combined ether layers were washed once with each of 1N hydrochloric acid, saturated sodium bicarbonate solution and brine
  6. dry with materialdried over magnesium sulfate
  7. customEvaporation

Sources & evidence

ORD record
ord-7bff0b51e2644d62bf52e6b5240dc318
Source dataset
uspto-grants-1996_07
Patent number
US05538988

Reaction notes

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