Sodium Carbonate → (S)-ethyl 2-(3,6-dimethyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-hydroxyacetate

HRID 926227Notes

Reaction equation

HRID 926227 reaction equation
[CH3:1][C:2]1[C:3]([C:21](=[O:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:4]([O:13][S:14]([C:17]([F:20])([F:19])[F:18])(=[O:16])=[O:15])[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH3:12])=[CH:7][CH:6]=2.B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@@H]2N1CCC2.[B]1OC2C(=CC=CC=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[CH3:1][C:2]1[C:3]([C@H:21]([OH:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:4]([O:13][S:14]([C:17]([F:19])([F:20])[F:18])(=[O:15])=[O:16])[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH3:12])=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 6327445BenzcatechinboraneHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 89676478Ethyl 2-(3,6-dimethyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-oxoacetate

Product 1

HCID 89681758(S)-ethyl 2-(3,6-dimethyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-hydroxyacetate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of ethyl 2-(3,6-dimethyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-oxoacetate (16.3 g, 40 mmol) in toluene (250 mL) cooled to an internal temperature of −40° C. was treated with (R)-(+)-2-methyl-CBS-oxazaborolidine (5.6 g, 20.1 mmol). Freshly distilled catecholborane (4.7 mL, 44.2 mmol) was diluted with toluene (20 mL) and the solution added dropwise to the reaction over 30 minutes to produce a clear yellow solution. After an additional 15 minutes, saturated Na2CO3 (300 mL) was added and the reaction allowed to warm to room temperature over 2.5 hours. The aqueous layer is extracted with EtOAc and the combined organics are washed with saturated Na2CO3 (3×300 mL), saturated NH4Cl (300 mL) and brine. Following drying over anhydrous MgSO4 and concentration in vacuo, the residue was purified using Isco silica gel column chromatography (10-75% EtOAc/hex) to produce (S)-ethyl 2-(3,6-dimethyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-hydroxyacetate that was determined to be 66% enantiomeric excess by HPLC analysis on a Chiralpak AS-H column with a 80:20 heptane/EtOH isocratic method. LCMS-ESI+ (m/z): [M+Na]+ calcd for C17H17F3O6SNa: 429.3. found: 429.3.

Workup

  1. additionthe solution added dropwise to the reaction over 30 minutes
  2. customto produce a clear yellow solution
  3. extractionThe aqueous layer is extracted with EtOAc
  4. washthe combined organics are washed with saturated Na2CO3 (3×300 mL), saturated NH4Cl (300 mL) and brine
  5. dry with materialFollowing drying over anhydrous MgSO4 and concentration in vacuo
  6. customthe residue was purified

Sources & evidence

ORD record
ord-2d76815d144b49f7b889f56374eb25e3
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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