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 1036685Notes

Reaction equation

HRID 1036685 reaction equation
[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

Participants

7

Reactant 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×

Product 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

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-7e7f6546efd94f559d2185ce072fc959
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

Loading…