Diisopropylethylamine → tert-butyl (2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylcarbamate

HRID 1036683Notes

Reaction equation

HRID 1036683 reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:11]([OH:13])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C.[CH3:49][N:50]1[CH2:54][C@H:53]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C@:52]2([CH2:65][CH2:64][CH2:63][NH:62][CH2:61]2)[C:51]1=[O:66].CN1C[C@@H](C2C=CC=CC=2)[C@@]2(CCCNC2)C1=O>CC#N.Cl>[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:11]([N:62]1[CH2:63][CH2:64][CH2:65][C:52]2([C:51](=[O:66])[N:50]([CH3:49])[CH2:54][CH:53]2[C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH2:61]1)=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 2733693(R)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanoic acidHCID 71060185(4S,5R)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one2×HCID 71060283(4R,5S)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one

Product 1

HCID 86674095tert-butyl (2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture comprising (R)-3-(benzyloxy)-2-(tert-butoxycarbonylamino)propanoic acid (Sigma-Aldrich) (1.052 g, 3.56 mmol) and ®T3P (50% in EtOAc) (4.16 ml, 7.12 mmol) in MeCN (20 mL) was treated dropwise with DIPEA (2.488 ml, 14.25 mmol). The resulting solution was stirred at room temperature for 30 minutes, then a racemic mixture of (4R,5S)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one and (4S,5R)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (Intermediate 1A) (1 g, 3.56 mmol) was added portionwise. The reaction mixture was stirred for 20 hours at room temperature. The reaction mixture was diluted with 0.1M HCl (20 mL) and extracted with DCM (20 mL). The aqueous phase was further extracted with DCM (3×20 mL). The combined organic portions were washed with a saturated solution of sodium bicarbonate (20 mL), water (20 mL), dried (MgSO4), and concentrated in vacuo to afford the title compound. No purification was performed on the title compound.

Workup

  1. additionwas added portionwise
  2. stirringThe reaction mixture was stirred for 20 hours at room temperature
  3. extractionextracted with DCM (20 mL)
  4. extractionThe aqueous phase was further extracted with DCM (3×20 mL)
  5. washThe combined organic portions were washed with a saturated solution of sodium bicarbonate (20 mL), water (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d8eb3aa6e5384a1a892868ecf4447f40
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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