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

HRID 1036671Notes

Reaction equation

HRID 1036671 reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:27])[C:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH3:18])[CH3:17])[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]2[C:39]3([CH2:44][CH2:43][CH2:42][NH:41][CH2:40]3)[C:38](=[O:45])[N:37]([CH3:46])[CH2:36]2)=[CH:31][CH:30]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CC#N.C(=O)(O)[O-].[Na+].C(Cl)Cl>[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:27])[C:16]([NH:19][C:20](=[O:21])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])([CH3:18])[CH3:17])[C:11]([N:41]1[CH2:42][CH2:43][CH2:44][C:39]2([C:38](=[O:45])[N:37]([CH3:46])[CH2:36][CH:35]2[C:32]2[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=2)[CH2:40]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 111923Propylphosphonic anhydrideHCID 10894202(R)-3-(Benzyloxy)-2-(2-((tert-butoxycarbonyl)amino)-2-methylpropanamido)propanoic acid2×HCID 710604314-(4-Fluorophenyl)-2-methyl-2,7-diazaspiro[4.5]decan-1-one

Product 1

HCID 71060154tert-butyl 1-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamateYield 97%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred solution of (R)-3-benzyloxy-2-(2-tert-butoxycarbonylamino-2-methylpropionylamino)-propionic acid (Intermediate 3A) (344 mg, 0.904 mmol) and 4-(4-fluorophenyl)-2-methyl-2,7-diazaspiro[4.5]decan-1-one (270 mg, 0.904 mmol) in MeCN (4 mL) was added dropwise a solution of ®T3P (50% in EtOAc) (1.055 ml, 1.807 mmol) at room temperature. The resulting colourless solution was stirred for 20 hours. The reaction mixture was diluted with saturated aqueous sodium bicarbonate solution (10 mL) and DCM (10 mL). The aqueous phase was separated and extracted using DCM (3×10 mL), the combined organic fractions were washed with 10% citric acid (10 mL), dried (MgSO4) and then concentrated under reduced pressure to afford tert-butyl 1-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate (546 mg, 97%) as a white amorphous solid.

Workup

  1. customThe aqueous phase was separated
  2. extractionextracted
  3. washthe combined organic fractions were washed with 10% citric acid (10 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3b92b0b621154d11ab8394b9e1c435b1
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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