Pyridine → (4-Tert-butyl-3-formylamino-phenyl)-carbamic acid benzyl ester

HRID 423857

Reaktionsgleichung

Reaktionsgleichung von HRID 423857
[CH2:1]([O:8][C:9](=[O:22])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])=[C:13]([NH2:21])[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:29](OC=O)(=[O:31])C>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:22])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([CH3:18])([CH3:19])[CH3:20])=[C:13]([NH:21][CH:29]=[O:31])[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 1049PyridineHCID 75269Acetic-formic anhydrideHCID 57896235(3-Amino-4-tert-butyl-phenyl)-carbamic acid benzyl ester

Produkt 1

HCID 57896237(4-Tert-butyl-3-formylamino-phenyl)-carbamic acid benzyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A solution of (3-amino-4-tert-butyl-phenyl)-carbamic acid benzyl ester (0.97 g, 3.25 mmol) and pyridine (0.43 mL, 5.25 mmol) in CH2Cl2 (7.5 mL) was cooled to 0° C., and a solution of formic-acetic anhydride (3.5 mmol, prepared by mixing formic acid (158 μL, 4.2 mmol, 1.3 equiv) and acetic anhydride (0.32 mL, 3.5 mmol, 1.1 eq.) neat and ageing for 1 hour) in CH2Cl2 (2.5 mL) was added dropwise over 2 min. After the addition was complete, the mixture was allowed to warm to room temperature, whereupon it deposited a precipitate, and the resulting slurry was stirred overnight. The mixture was washed with 1 M citric acid (2×20 mL), saturated aqueous sodium bicarbonate (20 mL), dried (Na2SO4), and filtered. The cloudy mixture deposited a thin bed of solid above the drying agent, HPLC analysis showed this to be the desired formamide. The filtrate was concentrated to approximately 5 mL, and diluted with hexane (15 mL) to precipitate further formamide. The drying agent (Na2SO4) was slurried with methanol (50 mL), filtered, and the filtrate combined with material from the CH2Cl2/hexane recrystallisation. The resultant mixture was concentrated to afford (4-tert-butyl-3-formylamino-phenyl)-carbamic acid benzyl ester as an off-white solid (650 mg, 50% over 2 steps). 1H and 13C NMR (CD3OD) show the product as a rotameric mixture. 1H NMR (400 MHz, CD3OD, rotameric) δ 08.27 (s, 1H-a), 8.17 (s, 1H-b), 7.42-7.26 (m, 8H), 5.17 (s, 1H-a), 5.15 (s, 1H-b), 4.86 (s, 2H), 1.37 (s, 9H-a), 1.36 (s, 9H-b)□; 13C NMR (100 MHz, CD3OD, rotameric) δ □1636.9, 163.5, 155.8, 141.40, 141.32, 139.37, 138.88, 138.22, 138.14, 136.4, 135.3, 129.68, 129.65, 129.31, 129.24, 129.19, 129.13, 128.94, 128.50, 121.4 (br), 118.7 (br), 67.80, 67.67, 35.78, 35.52, 31.65, 31.34; ESI-MS 327.5 m/z (MH+).

Aufarbeitung

  1. additionAfter the addition
  2. washThe mixture was washed with 1 M citric acid (2×20 mL), saturated aqueous sodium bicarbonate (20 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated to approximately 5 mL
  6. additiondiluted with hexane (15 mL)
  7. customto precipitate further formamide
  8. filtrationfiltered
  9. customthe filtrate combined with material from the CH2Cl2/hexane recrystallisation
  10. concentrationThe resultant mixture was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-cea2658fce2a486b87c7ef52d0977dd7
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101767B2

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