Hydrochloric Acid → HCID 89782120, compound

HRID 1056125Notes

Reaction equation

HRID 1056125 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C@@H:11]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:12]([OH:14])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])(=[O:40])[CH2:36][C:37]([O-:39])=O.[Cl-].[Mg+2].[Cl-].CC(C)([O-])C.[K+].Cl>C1COCC1.CCOCC>[CH2:1]([O:8][CH2:9][CH2:10][C@@H:11]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:12](=[O:14])[CH2:36][C:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([O:8][CH2:9][CH2:10][C@@H:11]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])/[C:37](/[OH:39])=[CH:36]/[C:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 5360315Magnesium ChlorideHCID 21883978Tert-butyl malonateHCID 23665647Potassium tert-butoxideHCID 44721364O-Benzyl-N-(tert-butoxycarbonyl)-D-homoserine

Product 2

HCID 89782120HCID 89782120, compoundHCID 89782265HCID 89782265, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Flask A: To a clear solution of (R)-4-(benzyloxy)-2-((tert-butoxycarbonyl)amino)butanoic acid (Combi-Blocks Inc, 5.01 g, 16.19 mmol) in THF (40 mL) at RT under nitrogen was added 1,1′-carbonyldiimidazole (3.94 g, 24.29 mmol) in one portion. Gas evolution observed and the reaction mixture was stirred 3 h. Flask B: To a cloudy mixture of mono-tert-butyl malonate (Sigma Aldrich, 4.99 mL, 32.4 mmol) and anhydrous magnesium chloride (Sigma Aldrich, 3.08 g, 32.4 mmol) in THF (60 mL) in a 3-necked 500 mL round-bottomed flask with a temperature probe at 2° C. was added potassium tert-butoxide (1.0M solution in THF, 32.4 mL, 32.4 mmol) slowly dropwise via addition funnel such that the temperature did not exceed 8° C. The resulting white suspension was stirred at RT for 2 h. The contents of Flask A was added to Flask B and the reaction mixture heated at 50° C. with stirring overnight (16 h). The reaction mixture was cooled to RT. The resulting white suspension was treated with 1N HCl (15 mL) to pH=7 and Et2O (60 mL) and washed with brine (30 mL), dried over anhydrous MgSO4, filtered, and concentrated affording crude (R)-tert-butyl 6-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-oxohexanoate and (R,Z)-tert-butyl 6-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-hydroxyhex-2-enoate (724a) as a viscous light yellow oil. m/z (ESI, +ve) 430.2 (M+Na)+.

Workup

  1. additionslowly dropwise via addition funnel such that the temperature
  2. customdid not exceed 8° C
  3. stirringThe resulting white suspension was stirred at RT for 2 h
  4. additionThe contents of Flask A was added to Flask B
  5. stirringwith stirring overnight (16 h)
  6. temperatureThe reaction mixture was cooled to RT
  7. washwashed with brine (30 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b9d960d9f321473283af9e4331d3d2b2
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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