Perchloric Acid → (S)-ethyl 2-tert-butoxy-2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

HRID 514105Notes

Reaction equation

HRID 514105 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[C:8]([O:13][S:14]([C:17]([F:20])([F:19])[F:18])(=[O:16])=[O:15])=[C:7]([C@H:21]([OH:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:6]([CH3:28])=[CH:5]2.Cl(O)(=O)(=O)=O>C(OC(=O)C)(C)(C)C>[C:4]([O:27][C@@H:21]([C:7]1[C:6]([CH3:28])=[CH:5][C:4]2[C:9](=[CH:10][C:11]([F:12])=[C:2]([Cl:1])[CH:3]=2)[C:8]=1[O:13][S:14]([C:17]([F:20])([F:19])[F:18])(=[O:15])=[O:16])[C:22]([O:24][CH2:25][CH3:26])=[O:23])([CH3:9])([CH3:5])[CH3:3]

Participants

4

Reactant 2

HCID 24247Perchloric AcidHCID 86691554(S)-ethyl 2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-hydroxyacetate

Product 1

HCID 86691553(S)-ethyl 2-tert-butoxy-2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetateYield 170.3%

Reagents, catalysts & solvents 1

HCID 10908tert-Butyl acetateSolvent

Procedure

To a solution of (S)-ethyl 2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-hydroxyacetate (4.44 g, 9.99 mmol) in tert-butylacetate (100 mL) was added 70% perchloric acid (1.20 mL, 19.98 mmol). The reaction mixture was stirred for 2.5 hours and quenched with solid sodium bicarbonate and stirred for 45 minutes. Water and solid sodium bicarbonate were carefully added and stirred for another 15 minutes. The mixture was diluted with ethyl acetate, washed with saturated bicarbonate solution (2×), brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes) to give an pale orange oil (4.26 g). 1H NMR (400 MHz, CDCl3) δ: 7.86 (d, J=7.2 Hz, 4H), 7.74 (d, J=10.2 Hz, 4H), 7.58 (s, 4H), 7.26 (s, 3H), 5.69 (s, 4H), 4.26-4.08 (m, 9H), 2.53 (s, 12H), 1.20 (s, 34H), 1.17 (t, J=7.1 Hz, 13H).

Workup

  1. customquenched with solid sodium bicarbonate
  2. stirringstirred for 45 minutes
  3. additionWater and solid sodium bicarbonate were carefully added
  4. stirringstirred for another 15 minutes
  5. additionThe mixture was diluted with ethyl acetate
  6. washwashed with saturated bicarbonate solution (2×), brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2aa4599889ad4e8d85862e08074e48e5
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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