Methyl Acetate → Methyl 2-(6-bromo-4-(1,1-dimethylethylsulfinamido)-2-phenylchroman-4-yl)acetate

HRID 1408820Notes

Reaction equation

HRID 1408820 reaction equation
[C:1]([O:4][CH3:5])(=[O:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[Br:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[O:21][CH:20]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:19][C:18]2=[N:31][S:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33]>C1COCC1>[Br:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[O:21][CH:20]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:19][C:18]2([CH2:2][C:1]([O:4][CH3:5])=[O:3])[NH:31][S:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33]

Participants

5

Reactant 3

HCID 6584Methyl AcetateHCID 2724682Lithium diisopropylamideHCID 67174725HCID 67174725, compound

Product 1

HCID 67173575Methyl 2-(6-bromo-4-(1,1-dimethylethylsulfinamido)-2-phenylchroman-4-yl)acetateYield 34.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of methyl acetate (383 mg, 0.41 mL, 5.17 mmol) in anhydrous THF (10 mL) at −78° C. under N2 atmosphere is added 2 M LDA solution in THF (3.4 mL, 6.8 mmol) dropwise, and the solution is stirred another 30 min at the same temperature after the addition. To this mixture is added TiCl(OiPr)3 (1.681 g, 6.45 mmol) dropwise. The mixture is then stirred another 30 min at −78° C. To this mixture is added a solution of N-(6-bromo-2-phenylchroman-4-ylidene)-2-methylpropane-2-sulfinamide (1.050 g, 2.58 mmol) in anhydrous THF (10 mL) dropwise within 30 min. The reaction mixture is stirred another 3 h at −78° C. then quenched with sat. aq. NH4Cl. The mixture is stirred 10 min after being warmed to rt and filtered through a pad of Celite, and washed with EA (80 mL). The filtrate is transferred to separating funnel and the separated organic phase is washed with brine, and dried over anhydrous Na2SO4, filtered and concentrated, and the residue is purified through chromatography on silica gel to afford methyl 2-(6-bromo-4-(1,1-dimethylethylsulfinamido)-2-phenylchroman-4-yl)acetate 427 mg as an oil. MS ESI+ve m/z 480 (M+H)+.

Workup

  1. additionafter the addition
  2. stirringThe mixture is then stirred another 30 min at −78° C
  3. stirringThe reaction mixture is stirred another 3 h at −78° C.
  4. customthen quenched with sat. aq. NH4Cl
  5. stirringThe mixture is stirred 10 min
  6. filtrationfiltered through a pad of Celite
  7. washwashed with EA (80 mL)
  8. customto separating funnel
  9. washthe separated organic phase is washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customthe residue is purified through chromatography on silica gel

Sources & evidence

ORD record
ord-72132d25825c4f2c8293b8c55089a6db
Source dataset
uspto-grants-2014_12
Patent number
US08921359B2

Reaction notes

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