Phosphate → (S)-benzyl 2-benzyl-2-(1-(benzyloxy)-3-(3-(benzyloxy)-4-hydroxyphenyl)-2-methyl-1-oxopropan-2-yl)hydrazinecarboxylate

HRID 62231Notes

Reaction equation

HRID 62231 reaction equation
O1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:6]([O:13][C:14]([NH:16][NH:17][C@@:18]([CH3:31])([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[C:25]([OH:30])[CH:24]=1)[C:19]([OH:21])=[O:20])=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.P([O-])([O-])([O-])=O.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:43](Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C>[CH2:2]([N:17]([C@@:18]([CH3:31])([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[C:25]([O:30][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:24]=1)[C:19]([O:21][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:20])[NH:16][C:14]([O:13][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:15])[C:3]1[CH:4]=[CH:3][CH:2]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 1061PhosphateHCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 131737186(2S)-3-(3,4-dihydroxyphenyl)-2-methyl-2-(2-phenylmethoxycarbonylhydrazinyl)propanoic acid;oxolane

Product 1

HCID 124130654(S)-benzyl 2-benzyl-2-(1-(benzyloxy)-3-(3-(benzyloxy)-4-hydroxyphenyl)-2-methyl-1-oxopropan-2-yl)hydrazinecarboxylateYield 9.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 500 mL round bottom flask were added (S)-2-(2-((benzyloxy)carbonyl)hydrazinyl)-3-(3,4-di hydroxyphenyl)-2-methylpropanoic acid compound with tetrahydrofuran (1:1), Compound 1, (10 g, 84 wt %, 19.42 mmol) and 100 mL DMF. Cesium carbonate (11.39 g, 35 mmol) was added, and the mixture was stirred at room temperature for 15 minutes. The mixture was cooled in an ice bath. Benzyl bromide (7.38 mL, 62.2 mmol) was added portionwise. The mixture was stirred in the ice bath overnight. The slurry was filtered, and the cake was washed with methyl t-butyl ether. The filtrate was mixed with water, and the layers were separated. The aqueous layer was extracted with methyl t-butyl ether. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated. The crude was purified by flash chromatography using a 220 g silica column (0-30% ethyl acetate in heptanes) to afford Compound 2 as a colorless thick oil (1.20 g, 9.8%).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. filtrationThe slurry was filtered
  3. washthe cake was washed with methyl t-butyl ether
  4. additionThe filtrate was mixed with water
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with methyl t-butyl ether
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customThe crude was purified by flash chromatography

Sources & evidence

ORD record
ord-10860cff39b14f60a1baa964fa78695c
Source dataset
uspto-grants-2016_09
Patent number
US09446059B2

Reaction notes

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