Reaktion #58607

Reaktionsgleichung

Hünig's base

α-chloroethyl chloroformate

compound 55

2-[1,1′Biphenyl]-2-yl-1-[4-(phenylmethyl)morpholin-2-yl]-1-tetrahydro-2H-pyran-4-ylethanol

→

56

2-[1,1′-Biphenyl]-2-yl-1-morpholin-2-yl-1-tetrahydro-2H-pyran 4-ylethanol hydrochloride

Lösungsmittel

DCM

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigePurification by ion exchange chromatography
2. 2
   Sonstigegives the free base of 56 as viscous oil (0.483 g)
3. 3
   Sonstigepurified by ion exchange chromatography

Vorschrift

The free base of 56 is obtained from 55 (0.588 g, 1.28 mmol), solid supported Hünig's base (0.72 g) and α-chloroethyl chloroformate (0.53 mL) in anhydrous DCM (20 mL) following General Procedure 3. Purification by ion exchange chromatography gives the free base of 56 as viscous oil (0.483 g), contaminated with a small amount of the N-protected compound 55. The residue is treated with an excess of reagents (1 eq), solid supported Hünig's base (0.36 g) and α-chloroethyl chloroformate (0.26 mL) in anhydrous DCM (20 mL) and methanol (20 mL) and purified by ion exchange chromatography to give the free base of 56 (0.432 g). Purification by preparative LCMS followed by conversion to its hydrochloride salt following General Procedure 4 gives 56 (0.280 g, 54%). MW 403.95; C23H29NO3.HCl; 1H NMR (CD3OD): δ 7.45-7.59 (1H, m), 7.10-7.35 (8H, m), 3.85 (1H, dd, 13 Hz, 3.5 Hz), 3.75 (1H, dd, 11.5 Hz, 3.5 Hz), 3.51-3.59 (3H, m), 2.83-3.12 (7H, m), 2.64 (1H, t, 12 Hz), 1.36-1.52 (2H, m), 1.02-1.21 (2H, m), 0.90-0.94 (1H, m); LCMS: (12 min method) m/z 368 [M−HCl+H]+, RT 4.6 min.

Quelle