Ethyl Acetate → tert-butyl (1S,2R)-1-{[(S)-tert-butylsulfinyl]amino}-7-fluoroindane-2-carboxylate

HRID 64427Notes

Reaction equation

HRID 64427 reaction equation
[C:1]([S@@:5](/[N:7]=[CH:8]/[C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:6])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl-].[NH4+].C(OCC)(=O)C>C1COCC1>[C:1]([S@@:5]([NH:7][C@@H:8]1[C:9]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[F:15])[CH2:16][C@H:17]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:6])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 90072963tert-butyl 3-[2-[(E)-[(S)-tert-butylsulfinyl]iminomethyl]-3-fluorophenyl]propanoate

Product 1

HCID 86713437tert-butyl (1S,2R)-1-{[(S)-tert-butylsulfinyl]amino}-7-fluoroindane-2-carboxylateYield 34.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1.122 g of tert-butyl 3-{2-[(E)-{[(S)-tert-butylsulfinyl]imino}methyl]-3-fluorophenyl}propanoate (compound of Preparation Example 129) in 26.7 ml of THF was added 9.5 ml of lithium bis(trimethylsilyl)amide (1 M THF solution) at −78° C., followed by stirring at the same temperature for 8.5 hours. To the reaction mixture were added a saturated aqueous ammonium chloride solution and ethyl acetate to carry out a layer separation operation. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 390 mg of tert-butyl (1S,2R)-1-{[(S)-tert-butylsulfinyl]amino}-7-fluoroindane-2-carboxylate (Preparation Example 113a), and 130 mg of each of tert-butyl (1R,2R)-1-{[(S)-tert-butylsulfinyl]amino}-7-fluoroindane-2-carboxylate and tert-butyl (1S,2S)-1-{[(S)-tert-butylsulfinyl]amino}-7-fluoroindane-2-carboxylate (Preparation Example 113b and Preparation Example 113c).

Workup

  1. customa layer separation operation
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ac76a4f7adbf4c518d195bea9c30fa78
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Reaction notes

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