D-Proline → dibenzyl 1-((2S)-1-hydroxy-3-(tetrahydro-2H-pyran-3-yl)propan-2-yl)hydrazine-1,2-dicarboxylate

HRID 452008

Reaction equation

HRID 452008 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][CH2:8][CH:9]=[O:10])[CH2:2]1.[N:11]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])=[N:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].C1CN[C@@H](C(O)=O)C1.[BH4-].[Na+]>CC#N.C(O)C>[OH:10][CH2:9][C@@H:8]([N:11]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[NH:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[CH2:7][CH:3]1[CH2:4][CH2:5][CH2:6][O:1][CH2:2]1

Participants

7

Reactant 4

HCID 8988D-ProlineHCID 755571,2-Bis(phenylmethyl) 1,2-diazenedicarboxylateHCID 4311764Sodium borohydrideHCID 15676001Tetrahydro-2H-pyran-3-propanal

Product 1

HCID 58017413dibenzyl 1-((2S)-1-hydroxy-3-(tetrahydro-2H-pyran-3-yl)propan-2-yl)hydrazine-1,2-dicarboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-(tetrahydro-2H-pyran-3-yl)propanal (8.25 g, 0.058 mol) and dibenzyl azodicarboxylate (94%, 12.3 g, 0.041 mol) in MeCN (250 mL) at 0° C. was added (R-proline) (0.47 g, 0.0041 mol). After stirring the mixture at 0° C. for 15 hr. ethanol (100 mL) and NaBH4 (1.56 g, 0.041 mol) was added, and the mixture was stirred at 0° C. for 40 min. The reaction was quenched by slow addition of 10% aqueous citric acid (15 ml), and the whole solution was concentrated in vacuo. This residue was diluted with EtOAc (200 ml), washed with saturated brine (1×50 mL), dried over Na2SO4, and concentrated in vacuo to give the crude product, which was purified through column chromatography to give dibenzyl 1-((2S)-1-hydroxy-3-(tetrahydro-2H-pyran-3-yl)propan-2-yl)hydrazine-1,2-dicarboxylate (14.68 g, 81%).

Workup

  1. stirringthe mixture was stirred at 0° C. for 40 min
  2. customThe reaction was quenched by slow addition of 10% aqueous citric acid (15 ml)
  3. concentrationthe whole solution was concentrated in vacuo
  4. additionThis residue was diluted with EtOAc (200 ml)
  5. washwashed with saturated brine (1×50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give the crude product, which
  9. customwas purified through column chromatography

Sources & evidence

ORD record
ord-05708893fea3414699cd85f2ea037a9c
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Linked notes

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