Diisopropylethylamine → tert-butyl (R)-4-hydroxy-1-((4S,5R)-2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxobutan-2-ylcarbamate

HRID 1036695Notes

Reaction equation

HRID 1036695 reaction equation
[CH3:1][N:2]1[CH2:6][CH:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]2([CH2:17][CH2:16][CH2:15][NH:14][CH2:13]2)[C:3]1=[O:18].[C:19]([O:23][C:24]([NH:26][C@H:27]([CH2:31][CH2:32][OH:33])[C:28](O)=[O:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(C(C)C)CC)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C(#N)C.O>[OH:33][CH2:32][CH2:31][C@@H:27]([NH:26][C:24](=[O:25])[O:23][C:19]([CH3:21])([CH3:20])[CH3:22])[C:28]([N:14]1[CH2:15][CH2:16][CH2:17][C@:4]2([C:3](=[O:18])[N:2]([CH3:1])[CH2:6][C@H:5]2[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:13]1)=[O:29]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 13066456Boc-d-homoserineHCID 710604122-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one

Product 1

HCID 86674099tert-butyl (R)-4-hydroxy-1-((4S,5R)-2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxobutan-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (100 mg; 0.409 mmol) was solubilised in acetonitrile (1.4 ml). (R)-2-(Tert-butoxycarbonylamino)-4-hydroxybutanoic acid (90 mg; 0.409 mmol) was added followed by diisopropylethylamine (0.286 ml; 1.637 mmol). ®T3P (50% solution in ethyl acetate) (0.478 ml; 0.819 mmol) was added and the mixture stirred at RT for 2 hr. The reaction was diluted with water and extracted with EtOAc; the organics were combined and washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica eluting with 0-10% MeOH in DCM with ammonia to afford tert-butyl (R)-4-hydroxy-1-((4S,5R)-2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxobutan-2-ylcarbamate.

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on silica eluting with 0-10% MeOH in DCM with ammonia

Sources & evidence

ORD record
ord-0c4031b97c984e359d03c8c5c0f1403d
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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