4-Methylmorpholine → [(1R,2R)-1-(3-fluoro-azetidine-1-carbonyl)-2-hydroxy-propyl]-carbamic acid 9H-fluoren-9-ylmethyl ester

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Fmoc-D-allo-Thr-OH	HCID 6992534	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	3-fluoroazetidine Hydrochloride	HCID 10125054	—
Solvent	Acetonitrile	HCID 6342	—
Product	[(1R,2R)-1-(3-fluoro-azetidine-1-carbonyl)-2-hydroxy-propyl]-carbamic acid 9H-fluoren-9-ylmethyl ester	HCID 71279979	52.1%

Reaction Steps

A 25 mL round-bottomed flask was charged with (2R,3R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-hydroxybutanoic acid (184 mg, 0.54 mmol), 3-fluoroazetidine hydrochloride (66 mg, 0.59 mmol), and HATU (242 mg, 0.64 mmol). Then added acetonitrile (1.1 mL) followed by N,N-diisopropylethylamine (0.20 mL, 1.1 mmol) and N-methylmorpholine (0.05 mL, 0.45 mmol). The reaction mixture was stirred at room temperature overnight then concentrated. The crude solid was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 10-80% EtOAc) to afford 112 mg (52%) of [(1R,2R)-1-(3-fluoro-azetidine-1-carbonyl)-2-hydroxy-propyl]-carbamic acid 9H-fluoren-9-ylmethyl ester as a white solid. MS: [M+H]+=399.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08658646B2
Source dataset	uspto-grants-2014_02
ORD ID	ord-6db0ead717074accb339865d5d07ca5b
Source note	uspto-grants-2014_02