Triphenylphosphine → 5-bromo-3-[2(R)-tert-butoxycarbonylamino-2-cyclohexylethyl]-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

HRID 1790071Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1790071
[CH:1]1([CH:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:8]O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:18][C:19]1[C:20](=[O:36])[NH:21][C:22](=[O:35])[N:23]([CH2:26][C:27]2[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=2[F:34])[C:24]=1[CH3:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>C1COCC1>[Br:18][C:19]1[C:20](=[O:36])[N:21]([CH2:8][C@H:7]([NH:10][C:11]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:17])[CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:22](=[O:35])[N:23]([CH2:26][C:27]2[C:28]([F:34])=[CH:29][CH:30]=[CH:31][C:32]=2[F:33])[C:24]=1[CH3:25]

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 120945185-Bromo-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dioneHCID 22037861Tert-butyl N-(1-cyclohexyl-2-hydroxyethyl)carbamate

Produkt 1

HCID 210184025-bromo-3-[2(R)-tert-butoxycarbonylamino-2-cyclohexylethyl]-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dioneAusbeute 95,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 1-cyclohexyl-2-hydroxyethylcarbamate 4a (638 mg, 2.62 mmol) in THF (10 mL) was treated with 5-bromo-1-(2,6-difluorobenzyl)-6-methylpyrimidine-2,4(1H,3H)-dione 1d.1 (869 mg, 2.62 mmol) and triphenylphosphine (1.03 g, 3.93 mmol) at ambient temperature, then di-tert-butylazodicarboxylate (906 mg, 3.93 mmol) was introduced. The reaction mixture was stirred at ambient temperature for 16 hours and volatiles were evaporated. The residue was partitioned between saturated NaHCO3/H2O and EtOAc. The organic layer was dried (sodium sulfate), evaporated, and purified by flash chromatography (silica, 25% EtOAc/hexanes) to give compound 2b (1.39 g, 95.4%). MS (CI) m/z 456.10, 458.10 (MH+-Boc).

Aufarbeitung

  1. customvolatiles were evaporated
  2. customThe residue was partitioned between saturated NaHCO3/H2O and EtOAc
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. customevaporated
  5. custompurified by flash chromatography (silica, 25% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-4537ae6cd773424db4990e693acd9612
Quelldatensatz
uspto-grants-2006_07
Patentnummer
US07071200B2

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