The Synaptic Leap

2-Boc-1,2,3,4-tetrahydroisoquinoline

Submitted by Althea Tsang and Matthew H. Todd, School of Chemistry, University of Sydney, NSW 2006, Australia. Checked by Victor Sun, Lakshmi Raj Baratha, Soo-Jean Park, same address.

Preparation of Boc-THIQ

To 1,2,3,4-tetrahydroisoquinoline (2.00 g, 15.0 mmol) in dichloromethane (10 mL), triethylamine (3.1 mL, 22.6 mmol, 1.5 eq) and 4-dimethylaminopyridine (0.180 g, 1.5 mmol, 0.1 eq) were added. Di-tert-butyl dicarbonate (4.92 g, 22.6 mmol, 1.5 eq) was added and the reaction mixture stirred at rt for 24 h. The reaction mixture was diluted with dichloromethane (50 mL), washed with water (50 mL) and the organic portions extracted, dried (MgSO₄) and concentrated in vacuo to give a bright yellow oil, which was purified by flash column chromatography (3:1 ethyl acetate:hexane) to give the product as a bright yellow oil (3.49 g, 99%)

TLC (hexane:ethyl acetate, 5:1) after 3.5 hours indicated only product and baseline spots. TLC after 23 h indicated slight appearance of second spot at Rf = 0.38.

Boc-THIQ TLC

¹H NMR (CDCl₃): δ 1.49 (9H, s, H⁹), 2.83 (2H, dd, J 5.8, 5.8, H⁴), 3.64 (2H, dd, J 5.8, 5.8, H³), 4.57 (2H, s, H¹), 7.05 – 7.35 (4H, m). IR (CHCl₃) ν_max/cm^-1 1682, 1419, 1173. m/z (ESI) 132.1 (100%). 

Reference: Reductive deprotection of allyl, benzyl and sulfonyl substituted alcohols, amines and amides using a naphthalene-catalyzed lithiation, E. Alonso, D. J. Ramon and M. Yus, Tetrahedron 1997, 53, 14355-14368.

(O=C(OC(C)(C)C)N2CC1=CC=CC=C1CC2)

(HTDOHIVUPFBSNR-UHFFFAOYSA-N)

Addenda:
1) Original procedure used 1 N HCl wash as well as sat. NaHCO3 wash. No column chromatography.
2) Dilute NaHCO3 wash used in above procedure, working equally well.
3) Column in 1:1 hexane:ethyl acetate works equally well.

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