4-Bromothioanisole → HCID 57227238, compound

HRID 367365Notes

Reaction equation

HRID 367365 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.[C:15]([C@@H:19]1[O:23][C:22](=[O:24])[C@:21]([CH2:26][CH3:27])([CH3:25])[O:20]1)([CH3:18])([CH3:17])[CH3:16]>C1COCC1.CCCCCC>[C:15]([C@@H:19]1[O:23][C:22]([C:2]2[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][CH:3]=2)([OH:24])[C@@:21]([CH2:26][CH3:27])([CH3:25])[O:20]1)([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 660374-BromothioanisoleHCID 12860595HCID 12860595, compoundHCID 178418339Butyllithium

Product 1

HCID 57227238HCID 57227238, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-50 °C

Procedure

A solution of 4-bromothioanisole (48.5 g) in THF (600 mL) was cooled to -70° C. and a 2.5M solution of n-butyllithium in hexane (96 mL) was slowly added over 20 min. The resulting suspension was stirred for 1 h allowing the temperature of the cooling bath to raise to -50° C. It was then cooled back to -70° C. and a solution of dioxolanone from Step 2 (29.8 g) in TBF (100 mL) was added dropwise over 30 min. The reaction was allowed to proceed for another 30 min. and then quenched with AcOH (23 mL) always at -70° C. The reaction mixture was allowed to warm to r.t., diluted with a 25% aqueous solution of NH4OAc and extracted with EtOAc (2 L). The organic layer was dried over MgSO4 and concentrated. The resulting crude product was purified by flash chromatography (2→3→5→7% EtOAc in hexane) to give a light yellow solid. 1H NMR(CD3COCD3): mixture of diastereomers δ0.50 (0.5H, m), 0.68 (1.5H, s), 0.72 (1.5H, t), 0.97 (1.5H, t), 0.98 (9H, s), 1.38 (1.5H, s), 1.52 m), 1.68 (0.5H, m), 2.10 (0.5H, m), 2.48 (3H, 2s), 4.85 (1H, s, OH), 5.01 (0.5H, s), 5.32 (0.5H, s), 7.22-7.30 (2H, m), 7.50 (2H, dd).

Workup

  1. temperatureIt was then cooled back to -70° C.
  2. waitto proceed for another 30 min.
  3. customquenched with AcOH (23 mL) always at -70° C
  4. temperatureto warm to r.t.
  5. additiondiluted with a 25% aqueous solution of NH4OAc
  6. extractionextracted with EtOAc (2 L)
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationconcentrated
  9. customThe resulting crude product was purified by flash chromatography (2→3→5→7% EtOAc in hexane)
  10. customto give a light yellow solid

Sources & evidence

ORD record
ord-1dd647860fcd4dfe8628356b607dbc4b
Source dataset
uspto-grants-2000_10
Patent number
US06133292

Reaction notes

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