Cyclobutanecarbonyl chloride → (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(cyclobutanecarboxamido)propanoic acid

HRID 625855Notes

Reaction equation

HRID 625855 reaction equation
[CH:1]1([C:5](Cl)=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH:8]1[C:20]2[CH:19]([CH2:21][O:22][C:23]([NH:25][C@@H:26]([CH2:30][NH2:31])[C:27]([OH:29])=[O:28])=[O:24])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]=2[CH:11]=[CH:10][CH:9]=1>C1COCC1.[OH-].[Na+]>[CH:17]1[C:18]2[CH:19]([CH2:21][O:22][C:23]([NH:25][C@@H:26]([CH2:30][NH:31][C:5]([CH:1]3[CH2:4][CH2:3][CH2:2]3)=[O:6])[C:27]([OH:29])=[O:28])=[O:24])[C:20]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13]=2[CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 2

HCID 78705Cyclobutanecarbonyl chlorideHCID 688638Fmoc-Dap-OH

Product 1

HCID 90457582(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(cyclobutanecarboxamido)propanoic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent2×

Procedure

Cyclobutanecarbonyl chloride (72.7 mg, 0.613 mmol) and NaOH (0.735 mL, 0.735 mmol) were dropped at the same time to a stirred solution of (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-aminopropanoic acid (200 mg, 0.613 mmol) in THF (1.5 mL) and NaOH (1N, 0.8 mL) at 0° C. The reaction mixture was allowed to stir at rt for 1 h at which time LC-MS showed the desired product peak. The reaction solution was acidified with 1N HCl and extracted with EtOAc (60 mL×1). The crude was purified via flash chromatography (ISCO, silica gel, 12 g column; flow rate 30 mL/min, 100% DCM to 20% MeOH/DCM). Fractions containing the desired product were combined and dried via centrifugal evaporation to provide the title compound (156 mg, 61%).

Sources & evidence

ORD record
ord-d9c27b0b6f074a73a7d4ea55596535e2
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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