Diisopropylethylamine → 2-[1,1'-Biphenyl]-2-yl-1-cyclopentyl-1-morpholin-2-ylethanol hydrochloride

HRID 30326Notes

Reaction equation

HRID 30326 reaction equation
[C:1]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([CH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1)([CH:10]1[O:15][CH2:14][CH2:13][N:12](CC2C=CC=CC=2)[CH2:11]1)[OH:9].CCN(C(C)C)C(C)C.[Cl:43]C(OC(Cl)C)=O>C(Cl)Cl>[ClH:43].[C:1]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([CH:23]1[CH2:24][CH2:25][CH2:26][CH2:27]1)([CH:10]1[O:15][CH2:14][CH2:13][NH:12][CH2:11]1)[OH:9]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 597892882-[1,1'-Biphenyl]-2-yl-1-cyclopentyl-1-[4-(phenylmethyl)morpholin-2-yl]ethanol

Product 1

HCID 684360182-[1,1'-Biphenyl]-2-yl-1-cyclopentyl-1-morpholin-2-ylethanol hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The free base of 48 is prepared from 47 (1.75 g, 3.95 mmol), solid supported Hünig's base (2.22 g) and α-chloroethyl chloroformate (1.62 mL) in anhydrous DCM (30 mL) following General Procedure 3. Purification by ion exchange chromatography followed by flash column chromatography (eluent, MeOH/DCM 1/99 to 20/80 [v/v]) gives the free base as a viscous oil (805 mg, 58%) which is converted into 48 following General Procedure 4. MW 387.95; C23H29NO2.HCl; 1H NMR (CD3OD): δ 7.66-7.40 (1H, m) 7.19-7.47 (8H, m), 3.92 (1H, dd, 13 Hz, 3.5 Hz), 3.59-3.67 (2H, m), 3.05-3.16 (4H, m), 2.93 (1H, td, 13 Hz, 3.5 Hz,), 2.59 (1H, t, 12 Hz), 1.98-1.88 (1H, m), 1.55-1.19 (8H, m); LCMS: (12 minute method) m/z 351 [M−HCl+H]+, RT 5.68 min.

Workup

  1. customPurification by ion exchange chromatography

Sources & evidence

ORD record
ord-1638e1e420454f05a48fbbf6f0f6cc7c
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Reaction notes

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