Diisopropylethylamine → 2-[1,1'-Biphenyl]-2-yl-1-morpholin-2-yl-1-tetrahydro-2H-pyran 4-ylethanol hydrochloride

HRID 30329

Reaction equation

HRID 30329 reaction equation
[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([CH:16]1[O:21][CH2:20][CH2:19][N:18](CC2C=CC=CC=2)[CH2:17]1)([CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[OH:9].CCN(C(C)C)C(C)C.[Cl:44]C(OC(Cl)C)=O>C(Cl)Cl.CO>[ClH:44].[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([CH:16]1[O:21][CH2:20][CH2:19][NH:18][CH2:17]1)([CH:10]1[CH2:11][CH2:12][O:13][CH2:14][CH2:15]1)[OH:9]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 588549072-[1,1'Biphenyl]-2-yl-1-[4-(phenylmethyl)morpholin-2-yl]-1-tetrahydro-2H-pyran-4-ylethanol

Product 1

HCID 684351162-[1,1'-Biphenyl]-2-yl-1-morpholin-2-yl-1-tetrahydro-2H-pyran 4-ylethanol hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  1. customPurification by ion exchange chromatography
  2. customgives the free base of 56 as viscous oil (0.483 g)
  3. custompurified by ion exchange chromatography

Sources & evidence

ORD record
ord-fcc386fbce5f4465b0a62102e3a49dd4
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Linked notes

Loading…