Triphenylphosphine → 6-[(4-Fluoro-3-methylphenoxy)methyl]-1-benzyl-2-methylazepane

HRID 467479Notes

Reaction equation

[CH2:1]([N:8]1[CH:14]([CH3:15])[CH2:13][CH2:12][CH2:11][CH:10]([CH2:16][OH:17])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22](O)=[CH:21][C:20]=1[CH3:26].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>ClCCl>[F:18][C:19]1[CH:24]=[CH:23][C:22]([O:17][CH2:16][CH:10]2[CH2:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:14]([CH3:15])[CH2:13][CH2:12][CH2:11]2)=[CH:21][C:20]=1[CH3:26]

Participants

Conditions

Temperature: 23 °C

Procedure

A mixture of (1-benzyl-7-methylazepan-3-yl)methanol (2-5, 500 mg, 2.1 mmol, 1.0 equiv), 4-fluoro-3-methylphenol (300 mg, 2.4 mmol, 1.1 equiv), and PS-triphenyl phosphine resin (1.2 g, 2.4 mmol, 1.1 equiv) in dichloromethane (25 mL) was treated with DIAD (0.46 mL, 480 mg, 2.4 mmol, 1.1 equiv) and the resulting suspension was stirred for 16 hours at 23° C. The mixture was filtered and filtrate was concentrated. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes gradient) to yield 6-[(4-fluoro-3-methylphenoxy)methyl]-1-benzyl-2-methylazepane (2-6) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.37 (m, 5H), 6.86 (m, 1H), 6.55 (m, 2H), 3.72-1.75 (m, 20H). LRMS m/z (M+H) 342.3 found, 242.2 required.

Workup

filtrationThe mixture was filtered
concentrationfiltrate was concentrated
customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record: ord-32c01b6a9d714b4991b1ec293b00f8f0
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623863B2

Reaction notes

Loading…