Methanol → HCID 68541571, compound

HRID 1446757Notes

Reaction equation

HRID 1446757 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]#[N:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.CO.O1CCOCC1.[C:22]([O:26][C:27](=O)[O:28]C(C)(C)C)([CH3:25])([CH3:24])[CH3:23]>C1COCC1.ClCCl.C(OCC)(=O)C>[C:22]([O:26][C:27](=[O:28])[NH:13][CH2:12][CH2:11][S:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)(=[O:9])=[O:10])([CH3:25])([CH3:24])[CH3:23]

Participants

8

Reactant 4

HCID 887Methanol2×HCID 312751,4-DioxaneHCID 613538(4-Bromobenzene-1-sulfonyl)acetonitrileHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) ester

Product 1

HCID 68541571HCID 68541571, compoundYield 28.8%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Suspend (4-Bromobenzenesulfonyl)-acetonitrile (10.41 g, 40.02 mmol) in THF and cooled to 0° C., and add borane-dimethylsulfide complex (10 M, 12 mL, 120 mmol) to the suspension which is allowed to slowly warm to ambient temperature. The next day, quench the reaction with a slow addition of methanol until off-gassing ceases. Concentrate the reaction to dryness and add more methanol and bring to reflux for 3 hours. Concentrate the reaction to dryness, then dissolve in dichloromethane and extract with 1 N HCl (2×150 mL). Make the acidic aqueous extracts basic using 50% NaOH and Na2CO3. Treat the aqueous solution with dioxane (500 mL) and di-tertbutylcarbonate (10.91 g, 50.00 mmol) for 3 days. Dilute the reaction with dichloromethane, separate the layers and re-extract the aqueous with dichloromethane. Wash the organic extracts with aqueous saturated sodium chloride, dry over MgSO4, filter and concentrate to yield a crude oil. Chromatograph on silica utilizing (0→5→8%) ethyl acetate in dichloromethane to afford the title compound (4.20 g, 11.53 mmol). MS(ES), m/z 307/309 (M+1 minus t-butyl).

Workup

  1. additionadd borane-dimethylsulfide complex (10 M, 12 mL, 120 mmol) to the suspension which
  2. temperatureto slowly warm to ambient temperature
  3. customThe next day, quench
  4. customthe reaction
  5. concentrationConcentrate
  6. customthe reaction to dryness
  7. temperatureto reflux for 3 hours
  8. concentrationConcentrate
  9. customthe reaction to dryness
  10. extractionextract with 1 N HCl (2×150 mL)
  11. additionDilute
  12. customseparate the layers
  13. extractionre-extract the aqueous with dichloromethane
  14. washWash the organic extracts with aqueous saturated sodium chloride
  15. dry with materialdry over MgSO4
  16. filtrationfilter
  17. concentrationconcentrate
  18. customto yield a crude oil

Sources & evidence

ORD record
ord-7a0b9a7c1bbf4f7980f19a0a6966f6b6
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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