Diisopropylethylamine → 1-(4-Fluoro[1,1'-biphenyl]-2-yl)-4-methyl-2-morpholin-2-ylpentan-2-ol hydrochloride

HRID 30325Notes

Reaction equation

HRID 30325 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:4]([CH2:14][C:15]([CH:21]2[O:26][CH2:25][CH2:24][N:23](CC3C=CC=CC=3)[CH2:22]2)([OH:20])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:3]=1.[Cl:34]C(OC(Cl)C)=O.CCN(C(C)C)C(C)C>C(Cl)Cl>[ClH:34].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[C:4]([CH2:14][C:15]([CH:21]2[O:26][CH2:25][CH2:24][NH:23][CH2:22]2)([OH:20])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 597893194-Fluoro[1,1'-biphenyl]-2-yl-4-methyl-2-[4-(phenylmethyl)morpholin-2-yl]pentan-2-ol

Product 1

HCID 684356251-(4-Fluoro[1,1'-biphenyl]-2-yl)-4-methyl-2-morpholin-2-ylpentan-2-ol hydrochlorideYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

40 is prepared from 39 (1.31 g, 2.92 mmol), α-chloroethyl chloroformate (0.9 mL) and solid supported Hünig's base (1.64 g) in anhydrous DCM (30 mL) following General Procedure 3. Purification by ion exchange ion exchange chromatography gives the free base of 40 as a viscous oil (0.71 g, 62%). After further purification using UV-guided preparative LCMS, the hydrochloride salt 40 (0.451 g, 39%) is obtained following General Procedure 4. MW 393.95; C22H28FNO2. HCl; 1H NMR (DMSO-d6): δ 9.16 (1H, s), 8.98 (1H, s), 7.44-7.32 (4H, m), 7.23-7.06 (4H, m), 3.83 (1H, dd, 12 Hz, 3 Hz), 3.59-3.50 (3H, m), 3.18 (1H, d, 12.5 Hz), 3.08 (1H, d, 12.5 Hz), 2.92-2.67 (4H, m), 1.54-1.40 (1H, m), 1.03 (1H, dd, 14.5 Hz, 5 Hz), 0.88 (1H, dd, 14.5 Hz, 6.5 Hz), 0.74 (3H, d, 6.5 Hz), 0.67 (3H, d, 6.5 Hz); LCMS: (12 minute method) m/z 358 [M−HCl+H]+ RT 5.47 min.

Workup

  1. customPurification by ion exchange ion exchange chromatography

Sources & evidence

ORD record
ord-590c0c40528548c2a410116fb5e3f261
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Reaction notes

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