Triethylamine → 4-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-thiophen-2-yl]-piperidine-1 carboxylic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	Triethylamine	HCID 8471	—
Reactant	1,3,3-Trimethyl-6-azabicyclo(3.2.1)octane	HCID 103787	—
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	5-(1-(Tert-butoxycarbonyl)piperidin-4-yl)thiophene-3-carboxylic acid	HCID 59542480	—
Solvent	Acetonitrile	HCID 6342	—
Product	4-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-thiophen-2-yl]-piperidine-1 carboxylic acid tert-butyl ester	HCID 59542553	92.4%

Reaction Steps

4-(4-Carboxy-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester (0.1 g, 0.32 mmol) was dissolved in acetonitrile (2 mL). Triethylamine (0.96 mmol), 1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane (0.35 mmol) and HATU (0.35 mmol) were added and the reaction stirred at room temperature for 18 hours. The solvent was evaporated and the residue was purified by flash chromatography, eluting with 0-50% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.132 g). 1H NMR (400 MHz, CHCl3-d; 80° C.); □ 7.6 (s, 1H), 7.0 (s, 1H), 4.3 (m, 1H), 4.0 (m, 2H), 3.4 (m, 1H), 3.2 (m, 1H), 3.0 (m, 1H), 2.9 (m, 1.9 (m, 2H), 1.7 (m, 1H), 1.6-0.9 (m, 26H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08362008B2
Source dataset	uspto-grants-2013_01
ORD ID	ord-108851e33f9c4a8aa57dd99909e5938b
Source note	uspto-grants-2013_01