Acetic Acid → Tert-butyl [3-(cyclopropylamino)phenyl]carbamate

HRID 1800714Notes

Reaction equation

HRID 1800714 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([NH2:14])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.C(O[C:23]1(O[Si](C)(C)C)[CH2:25][CH2:24]1)C.[BH4-].[Na+].C(=O)([O-])O.[Na+]>CO.O1CCCC1>[CH:23]1([NH:14][C:10]2[CH:9]=[C:8]([NH:7][C:6](=[O:15])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:13]=[CH:12][CH:11]=2)[CH2:25][CH2:24]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 4311764Sodium borohydrideHCID 12877220tert-butyl N-(3-aminophenyl)carbamate

Product 1

HCID 86646082Tert-butyl [3-(cyclopropylamino)phenyl]carbamateYield 59.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl(3-aminophenyl)carbamate (6.91 g, 33.2 mmol) in methanol (30 mL) were added acetic acid (5.69 mL, 99.5 mmol) and [(1-ethoxycyclopropyl)oxy](trimethyl)silane (7.98 mL, 39.8 mmol), and the mixture was stirred at 60° C. for 4 hr. The reaction mixture was concentrated under reduced pressure. A solution of the obtained residue in tetrahydrofuran (20 mL) was added dropwise to a suspension of sodium tetrahydroborate (2.51 g, 66.4 mmol) and boron trifluoride diethyl ether complex (8.33 mL, 66.4 mmol) in tetrahydrofuran (30 mL) (the suspension was stirred in advance at room temperature for 1 hr) at 0° C. over 30 min, and the mixture was stirred at room temperature for 2.5 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (100 mL), and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with saturated brine (20 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5→90/10), and the fractions containing the object product were concentrated under reduced pressure to give the title compound (4.87 g, 59%) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringwas stirred in advance at room temperature for 1 hr) at 0° C. over 30 min
  3. stirringthe mixture was stirred at room temperature for 2.5 hr
  4. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layer was washed with saturated brine (20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe insoluble material was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5→90/10)
  10. additionthe fractions containing the object product
  11. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-2b9018f6d0564cdba7c3debed4af1728
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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