Ethylenediamine → 7-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-hept-5-enoic acid methyl ester

HRID 2052925Notes

Reaction equation

HRID 2052925 reaction equation
[BH4-].[Na+].C(N)CN.[CH3:7][O:8][C:9](=[O:25])[CH2:10][CH2:11][CH2:12][C:13]#[C:14][CH2:15][N:16]1[C:21](=[O:22])[CH2:20][CH2:19][CH2:18][C@@H:17]1[CH2:23][OH:24].[H][H]>C(O)C.[Ni](Cl)Cl>[CH3:7][O:8][C:9](=[O:25])[CH2:10][CH2:11][CH2:12][CH:13]=[CH:14][CH2:15][N:16]1[C:21](=[O:22])[CH2:20][CH2:19][CH2:18][C@@H:17]1[CH2:23][OH:24]

Participants

7

Reactant 4

HCID 3301EthylenediamineHCID 4311764Sodium borohydrideHCID 690212337-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 690228967-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-hept-5-enoic acid methyl esterYield 38.8%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 702EthanolSolvent2×

Procedure

95% Ethanol (0.5 mL) was added to a mixture of nickel (II) chloride (105 mg, 0.81 mmol) and sodium borohydride (15 mg, 0.40 mmol). The mixture immediately turned black. After 15 min at rt, ethylene diamine (86 μL, 1.29 mmol) was added. After 15 min at rt, a solution of 7-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester (from Example 1, step 3, 43.3 mg, 0.16 mmol) in 95% ethanol (1.0 mL) was added via cannula. A hydrogen atmosphere was established by evacuating and refilling with hydrogen (3×) and the reaction mixture was stirred under a balloon of hydrogen for 19 h. The reaction mixture was filtered through celite, washing with ethanol, and the filtrate was concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient) afforded 16.7 mg (38%) of 7-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-hept-5-enoic acid methyl ester.

Workup

  1. waitAfter 15 min at rt
  2. customby evacuating
  3. filtrationThe reaction mixture was filtered through celite
  4. washwashing with ethanol
  5. concentrationthe filtrate was concentrated in vacuo
  6. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-8e2f6e94895e4ab49118871f4f4ac8d1
Source dataset
uspto-grants-2008_02
Patent number
US07326716B2

Reaction notes

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