Diisopropylethylamine → 2-adamantyl 2-((1R,2R)-2-(ethoxycarbonyl)cyclopropanecarbonyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
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	(1R,2R)-2-(ethoxycarbonyl)cyclopropane-1-carboxylic acid	HCID 11535603	—
Reactant	2-adamantyl 2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylate	HCID 25064613	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	2-adamantyl 2-((1R,2R)-2-(ethoxycarbonyl)cyclopropanecarbonyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylate	HCID 58137250	69.1%

Reaction Steps

2-Adamantyl 2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate (12 mg, 0.025 mmol), trans-2-(ethoxycarbonyl)cyclopropanecarboxylic acid (8 mg, 2.5 equiv), HATU (11 mg, 1.15 equiv), DIEA (13 μL, 3 equiv) were mixed with CH2Cl2 (2 mL) and put on shaker for 1 h at rt. The mixture was diluted with EtOAc (8 mL), washed with 3% aq HCl (2×3 mL), concentrated and purified by preparative HPLC to afford 2-adamantyl 2-((1R,2R)-2-(ethoxycarbonyl)cyclopropanecarbonyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate (9 mg, 69%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08927715B2
Source dataset	uspto-grants-2015_01
ORD ID	ord-a559383004f84c9dbb0511ec89b315a9
Source note	uspto-grants-2015_01