Diisopropylethylamine → tert-butyl (4R)-7,10,10,11,11-pentamethyl-4-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decane-7-carbonyl)-6-oxo-1-phenyl-2,9-dioxa-5-aza-10-siladodecan-7-ylcarbamate

HRID 1036685Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1036685
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:22])([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[NH2:50][C@H:51]([CH2:72][O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)[C:52]([N:54]1[CH2:71][CH2:70][CH2:69][C:56]2([C:60](=[O:61])[N:59]([CH3:62])[CH2:58][CH:57]2[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:55]1)=[O:53]>CN(C=O)C.Cl>[CH3:22][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])([CH2:13][O:14][Si:15]([CH3:17])([CH3:16])[C:18]([CH3:20])([CH3:21])[CH3:19])[C:10](=[O:12])[NH:50][C@@H:51]([C:52]([N:54]1[CH2:71][CH2:70][CH2:69][C:56]2([C:60](=[O:61])[N:59]([CH3:62])[CH2:58][CH:57]2[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:55]1)=[O:53])[CH2:72][O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 710604067-((R)-2-amino-3-(benzyloxy)propanoyl)-2-methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one2×HCID 866740972-(Tert-butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-2-methylpropanoic acid2×

Produkt 1

HCID 86674096tert-butyl (4R)-7,10,10,11,11-pentamethyl-4-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decane-7-carbonyl)-6-oxo-1-phenyl-2,9-dioxa-5-aza-10-siladodecan-7-ylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A mixture comprising 2-(tert-butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-2-methylpropanoic acid (intermediate from step 1) (311 mg, 0.934 mmol) and DIPEA (0.652 ml, 3.73 mmol) in DMF (5 mL) was treated with a solution of ®T3P (50% in EtOAc) (1.090 ml, 1.867 mmol) dropwise at room temperature. The resulting solution was stirred for 15 minutes, then 7-((R)-2-amino-3-(benzyloxy)propanoyl)-2-methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (intermediate from step 3) (500 mg, 0.934 mmol) in DMF (1 mL) was added dropwise at room temperature. The reaction mixture was stirred for 20 hours. The reaction mixture was diluted with 0.1M HCl (10 mL) and extracted with DCM (3×10 mL). The combined organic portions were washed with a saturated solution of sodium bicarbonate (10 mL), brine (10 mL), water (10 mL) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-70% EtOAc/iso-hexane afforded the title compound.

Aufarbeitung

  1. stirringThe reaction mixture was stirred for 20 hours
  2. extractionextracted with DCM (3×10 mL)
  3. washThe combined organic portions were washed with a saturated solution of sodium bicarbonate (10 mL), brine (10 mL), water (10 mL)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude product by chromatography on silica eluting with 0-70% EtOAc/iso-hexane

Quellen und Nachweise

ORD-Eintrag
ord-7e7f6546efd94f559d2185ce072fc959
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08546416B2

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