Sodium hydride → 11-[4-(2-Piperidin-1-yl-ethoxy)-benzyl]-6,11-dihydro-5-thia-11-aza-benzo[a]fluoren-8-ol

HRID 624499Notes

Reaction equation

HRID 624499 reaction equation
[H-].[Na+].C([Si](C)(C)[O:8][C:9]1[CH:10]=[C:11]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]1[C:16]3[CH:22]=[CH:23][CH:24]=[CH:25][C:15]=3[S:14][CH2:13][C:12]2=1)(C)(C)C.Cl[CH2:29][C:30]1[CH:44]=[CH:43][C:33]([O:34][CH2:35][CH2:36][N:37]2[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:32][CH:31]=1>CN(C=O)C>[N:37]1([CH2:36][CH2:35][O:34][C:33]2[CH:43]=[CH:44][C:30]([CH2:29][N:18]3[C:17]4[C:16]5[CH:22]=[CH:23][CH:24]=[CH:25][C:15]=5[S:14][CH2:13][C:12]=4[C:11]4[C:19]3=[CH:20][CH:21]=[C:9]([OH:8])[CH:10]=4)=[CH:31][CH:32]=2)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 98607864-(2-Piperidin-1-yl-ethoxy)benzyl chlorideHCID 596760598-(Tert-butyl-dimethyl-silanyloxy)-6,11-dihydro-5-thia-11-aza-benzo[a]fluorene

Product 1

HCID 1156901811-[4-(2-Piperidin-1-yl-ethoxy)-benzyl]-6,11-dihydro-5-thia-11-aza-benzo[a]fluoren-8-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (60%, 144 mg, 1.317 mmoL) was added into 8-(tert-butyl-dimethyl-silanyloxy)-6,11-dihydro-5-thia-11-aza-benzo[a]fluorene (440 mg, 1.197 mmoL) in DMF (5 mL) at 0° C. After 10 minutes, 1-[2-(4-chloromethyl-phenoxy)-ethyl]-piperidine (382 mg, 1.317 mmoL) was added dropwise into the reaction at 0° C. The reaction mixture was slowly warmed to room temperature over 2 hours. The reaction mixture was then partitioned between EtOAc and saturated NH4Cl. The aqueous phase was extracted two times with EtOAc. The organic layers from the two extractions were combined, washed with water, brine, dried over anhydrous Na2SO4, filtered and concentrated to yield a brown oil. The crude material (the oil) was then purified by column chromatography (silica gel, first EtOAc then CH2Cl2:MeOH 4:1 as eluent) to yield 8-(tert-butyl-dimethyl-silanyloxy)-11-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-6,11-dihydro-5-thia-11-aza-benzo[a]fluorine as a pale foam and 11-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-6,11-dihydro-5-thia-11-aza-benzo[a]fluoren-8-ol as a yellow solid.

Workup

  1. customThe reaction mixture was then partitioned between EtOAc and saturated NH4Cl
  2. extractionThe aqueous phase was extracted two times with EtOAc
  3. extractionThe organic layers from the two extractions
  4. washwashed with water, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a brown oil
  9. customThe crude material (the oil) was then purified by column chromatography (silica gel, first EtOAc

Sources & evidence

ORD record
ord-c27f82f8ef1f410fbf649b8aa562271b
Source dataset
uspto-grants-2016_04
Patent number
US09303037B2

Reaction notes

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