Hydrochloric Acid → HCID 89793963, compound

HRID 1056400Notes

Reaction equation

HRID 1056400 reaction equation
[CH3:1][CH2:2][C@@H:3]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:27]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])(=[O:32])[CH2:28]C([O-])=O.[Cl-].[Mg+2].[Cl-].CC(C)([O-])C.[K+].Cl>C1COCC1.O.CCOCC>[C:34]([O:33][C:27](=[O:32])[CH2:28][C:4](=[O:6])[C@H:3]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2][CH3:1])([CH3:37])([CH3:36])[CH3:35]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 2755936(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acidHCID 5360315Magnesium ChlorideHCID 21883978Tert-butyl malonateHCID 23665647Potassium tert-butoxide

Product 1

HCID 89793963HCID 89793963, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Flask B: To a clear solution of Boc-D-abu-oh (Bachem, 5.00 g, 24.60 mmol) in THF (40 mL) at RT under nitrogen was added 1,1′-carbonyldiimidazole (4.19 g, 25.8 mmol) in one portion. Gas evolution observed and the reaction was stirred for 2.5 h at RT. Flask A: To a mixture of mono-tert-butyl malonate (4.17 mL, 27.1 mmol) and anhydrous magnesium chloride (2.58 g, 27.1 mmol) in THF (100 mL) in a 500 mL 3-necked round-bottomed flask in an ice bath was added potassium tert-butoxide (1.0 M in THF, 27.1 mL, 27.1 mmol) slowly dropwise via addition funnel such that the temperature did not exceed 8° C. The resulting white suspension (milk-like) was stirred at RT for 2 h 30 min then the contents of flask B was added to flask A and the reaction mixture was heated at 50° C. overnight (16 h). The reaction mixture was treated with 1N HCl (15 mL) to pH=7 and then treated with Et2O (60 mL) and water (45 mL). The organic layer was separated, and washed brine (30 mL), dried over anhydrous MgSO4, filtered, and concentrated in vacuo to afford (R)-tert-butyl 4-((tert-butoxycarbonyl)amino)-3-oxohexanoate (505a) as a viscous light yellow oil. m/z (ESI, +ve) 324.2 (M+Na)+.

Workup

  1. additionslowly dropwise via addition funnel such that the temperature
  2. customdid not exceed 8° C
  3. stirringThe resulting white suspension (milk-like) was stirred at RT for 2 h 30 min
  4. additionthe contents of flask B was added to flask A and the reaction mixture
  5. temperaturewas heated at 50° C. overnight (16 h)
  6. customThe organic layer was separated
  7. washwashed brine (30 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-24b8a25fa75c4e0ca0ecf108eb53756f
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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