1-(Bromomethyl)-2-phenylbenzene → 1-[1,1'-Biphenyl]-2-yl-6,6,6-trifluoro-2-[4-(phenylmethyl)morpholin-2-yl]hexan-2-ol

HRID 30330

Reaction equation

HRID 30330 reaction equation
[F:1][C:2]([F:22])([F:21])[CH2:3][CH2:4][CH2:5][C:6]([CH:8]1[O:13][CH2:12][CH2:11][N:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)=[O:7].[C:23]1([C:29]2[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=2[CH2:31][Mg:32][Br:33])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[C:38]1([C:44]2[CH:51]=[CH:50][CH:49]=[CH:48][C:45]=2[CH2:46]Br)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>>[C:23]1([C:29]2[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=2[CH2:31][Mg:32][Br:33])[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1.[C:44]1([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:51]=[CH:50][CH:49]=[CH:48][C:45]=1[CH2:46][C:6]([CH:8]1[O:13][CH2:12][CH2:11][N:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)([OH:7])[CH2:5][CH2:4][CH2:3][C:2]([F:1])([F:21])[F:22]

Participants

5

Reactant 3

HCID 2633651-(Bromomethyl)-2-phenylbenzeneHCID 597892745,5,5-Trifluoro-1-[4-(phenylmethyl)morpholin-2-yl]pentan-1-oneHCID 178419666HCID 178419666, compound2×

Product 2

HCID 588548811-[1,1'-Biphenyl]-2-yl-6,6,6-trifluoro-2-[4-(phenylmethyl)morpholin-2-yl]hexan-2-olYield 28%HCID 178419666HCID 178419666, compound

Procedure

Compound 67 is prepared from 10 (0.853 g, 2.71 mmol) and 2-phenyl benzyl magnesium bromide (0.25 M solution in diethyl ether, 1.2 eq) following General Procedure 2. 2-Phenylbenzyl magnesium bromide is prepared from commercially available (Aldrich) 2-phenylbenzyl bromide following General Procedure 5. Further 2-phenyl benzyl magnesium bromide is added later (19.2 mL, 4.8 mmol). Purification by automated column chromatography (eluent, EtOAc/cyclohexane 20/80 to 40/60 [v/v]), followed by ion exchange chromatography gives 67 as a viscous oil (369 mg, 28%). MW 483.58; C29H32F3NO2; LCMS: (6 min method) m/z 484 [M+H]+, RT 4.26 min.

Workup

  1. customPurification by automated column chromatography (eluent, EtOAc/cyclohexane 20/80 to 40/60 [v/v])

Sources & evidence

ORD record
ord-8fdb77dd934b46c0b82cea73c3125b81
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Linked notes

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