Diethyl Ether → 4-[6-Benzyloxy-2-(4-fluoro-phenyl) naphthalen-1-yloxy]-benzaldehyde

HRID 1513866Notes

Reaction equation

[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([OH:21])=[C:16]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)[CH:15]=[CH:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.F[C:30]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1.C(OCC)C>CN1C(=O)CCC1>[CH2:3]([O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([O:21][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1)=[C:16]([C:22]1[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=1)[CH:15]=[CH:14]2)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 165 °C

Procedure

Add sodium hydride (400 mg, 10 mmol) into a solution of 6-benzyloxy-2-(4-fluoro-phenyl)-naphthalen-1-ol in NMP (40 mL). Add the above alkoxide suspension into a solution of 4-fluorobenzaldehyde (2 mL, 19 mmol) in NMP (30 mL) at 165° C. Heat at 165° C. for 1 hour. Cool and add buffer solution (pH=7, 10 mL). Add diethyl ether (1 L). Separate the layers and wash the aqueous layer with diethyl ether (2×200 mL). Combine the organic layers, dry with magnesium sulfate and concentrate in vacuo. Chromatograph the residue on a biotage column eluting the material with a step gradient of methanol/dichloromethane (0 to 10%) to obtain 2.9 g (70%) of 4-[6-benzyloxy-2-(4-fluoro-phenyl)-naphthalen-1-yloxy]-benzaldehyde.

Workup

temperatureCool
customSeparate the layers
washwash the aqueous layer with diethyl ether (2×200 mL)
dry with materialCombine the organic layers, dry with magnesium sulfate
concentrationconcentrate in vacuo
washChromatograph the residue on a biotage column eluting the material with a step gradient of methanol/dichloromethane (0 to 10%)

Sources & evidence

ORD record: ord-e095f571dadc4e15bb581e518e23e6ed
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217032B2

Reaction notes

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