1,2-Dichloroethane → (3R)-tert-butyl 3-(methoxy(methyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	1,2-Dichloroethane	HCID 11	—
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(3R)-2-[(tert-butoxy)carbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid	HCID 688607	—
Reactant	Methoxymethanamine hydrochloride	HCID 21959107	—
Solvent	Tetrahydrofuran	HCID 8028	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	(3R)-tert-butyl 3-(methoxy(methyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate	HCID 86597541	71.5%

Reaction Steps

Boc-D-Tic-OH (14.9 g, 53.7 mmol), methoxymethylamine hydrochloride (5.24 g, 53.7 mmol), EDC (11.3 g, 59.1 mmol); HOBT (7.98 g, 59.1 mmol), DIPEA (9.83 ml, 59.1 mmol) and THF (500 ml) are combined, and the resulting mixture is stirred for about 18 hours at r.t. under nitrogen. The mixture is stripped to dryness, and the residue is taken up in ethyl acetate. The resulting mixture is washed with 1M HCl, saturated NaHCO3 and brine, and then dried. Solvent is removed and the residue is chromatographed on normal phase using 1:1 ethylacetate/hexane to give about 12.3 g of Boc-D-Tic-NMeOMe (Weinreb amide).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07157463B2
Source dataset	uspto-grants-2007_01
ORD ID	ord-b5ebed1fb6df4e2680ba4587046d7198
Source note	uspto-grants-2007_01