Water → 1-(2-{4-[6-Benzyloxy-2-(4-fluoro-phenyl)-naphthalen-1-yloxy]-phenoxy}-ethyl)-azepane

HRID 1513877Notes

Reaction equation

HRID 1513877 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]([O:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)=[C:16]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[CH:15]=[CH:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.[N:37](=[CH:45][CH2:46]Cl)[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]Cl.O>CN(C=O)C.C(OCC)C>[CH2:3]([O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([O:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:46][CH2:45][N:37]3[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]3)=[CH:24][CH:23]=1)=[C:16]([C:29]1[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=1)[CH:15]=[CH:14]2)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 534452772-(hexamethyleneimino)ethyl chloride HClHCID 575525594-[6-Benzyloxy-2-(4-fluoro-phenyl)-naphthalen-1-yloxy]-phenol

Product 1

HCID 575525161-(2-{4-[6-Benzyloxy-2-(4-fluoro-phenyl)-naphthalen-1-yloxy]-phenoxy}-ethyl)-azepaneYield 66%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Add sodium hydride (324 mg, 8.0 mmol) into a solution of 4-[6-benzyloxy-2-(4-fluoro-phenyl)-naphthalen-1-yloxy]-phenol (1.18 g, 2.7 mmol) in DMF (10 mL) and stir for 20 minutes at room temperature. Add 2-(hexamethyleneimino)ethyl chloride hydrogen chloride (1.07 g, 5.4 mmol) and stir at room temperature for 12 hours. Add H2O (10 mL) and diethyl ether (100 mL). Separate layers and wash the aqueous layer with diethyl ether (2×50 mL). Combine organic layers, dry with magnesium sulfate and concentrate in vacuo. Purify the residue over silica gel, eluting the material with a step gradient of methanol/dichloromethane (0% to 10%), to obtain 1.0 g of the title compound (66%): mass spectrum (ion spray) m/z=562.3 (M+H).

Workup

  1. washSeparate layers and wash the aqueous layer with diethyl ether (2×50 mL)
  2. dry with materialCombine organic layers, dry with magnesium sulfate
  3. concentrationconcentrate in vacuo
  4. customPurify the residue over silica gel
  5. washeluting the material with a step gradient of methanol/dichloromethane (0% to 10%)

Sources & evidence

ORD record
ord-747415ac55f2401c8cc595bf32923145
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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