Oxalic Acid → Tert-butyl (5-bromopyrimidin-2-YL)carbamate

HRID 341322Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 341322
[C:1]([O:5][C:6]([N:8](C(OC(C)(C)C)=O)[C:9]1[N:14]=[CH:13][C:12]([Br:15])=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].C(O)(=O)C(O)=O>C(O)C.O>[Br:15][C:12]1[CH:13]=[N:14][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[N:10][CH:11]=1

Komponenten

6

Edukt 3

HCID 971Oxalic AcidHCID 14798Sodium HydroxideHCID 11977091tert-butyl N-(5-bromopyrimidin-2-yl)-N-((tert-butoxy)carbonyl)carbamate2×

Produkt 1

HCID 18549354Tert-butyl (5-bromopyrimidin-2-YL)carbamateAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

To a solution of 2-[bis(tert-butoxycarbonyl)amino]-5-bromopyrimidine 10 (216 kg crude, 460 mol, assuming quantitative yield in previous step) in anhydrous ethanol (1692 L) was slowly added a solution of sodium hydroxide (55.2 kg, 1380 mol) in water (344 L) while maintaining the temperature at 0-20° C. The mixture was stirred at that temperature until the content of 2-[bis(tert-butoxycarbonyl)-amino]-5-bromopyrimidine (10) was ≦0.5% by HPLC. The reaction mixture was cooled to 0-5° C. and the pH was adjusted to 7 by addition of oxalic acid (86.0 kg, 955 mol) while maintaining the temperature below 5° C. The mixture was then distilled under vacuum to a volume of 500-600 L while controlling the temperature below 50° C. Water (800 kg) was added and the mixture was stirred for 1 h. The solid was collected by filtration and stirred with water (2×500 L). The resulting solid was collected by filtration and dried under reduced pressure at 50° C. to afford tert-butyl 5-bromopyrimidin-2-ylcarbamate 11 (107 kg, 85% yield over two steps). 1H NMR (500 MHz, CDCl3) δ 8.63 (s, 2H), 8.12 (s, 1H), 1.55 (s, 9H). LCMS (ESI) m/z [M+H-Boc] 176

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to 0-5° C.
  2. temperaturewhile maintaining the temperature below 5° C
  3. distillationThe mixture was then distilled under vacuum to a volume of 500-600 L
  4. customthe temperature below 50° C
  5. additionWater (800 kg) was added
  6. filtrationThe solid was collected by filtration
  7. stirringstirred with water (2×500 L)
  8. filtrationThe resulting solid was collected by filtration
  9. customdried under reduced pressure at 50° C.

Quellen und Nachweise

ORD-Eintrag
ord-14c6b0cac68d45e581b875a85ea360f6
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895729B2

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