Piperidine → N-(4-Amino-2-benzyloxy-phenyl)-4-fluoro-2-hydroxy-benzamide

HRID 1354820Notes

Reaction equation

HRID 1354820 reaction equation
C1C2C(COC(=O)[NH:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:34])[C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[OH:33])=[C:20]([O:35][CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[CH:19]=3)C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1>C1COCC1.CN(C=O)C>[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:34])[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[OH:33])=[C:20]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:19]=1

Participants

5

Reactant 2

HCID 8082PiperidineHCID 58865711HCID 58865711, compound

Product 1

HCID 21104164N-(4-Amino-2-benzyloxy-phenyl)-4-fluoro-2-hydroxy-benzamideYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

[3-Benzyloxy-4-(4-fluoro-2-hydroxy-benzoylamino)-phenyl]-carbamic acid 9H-fluoren-9-yl-methyl ester (75) (0.192 g, 0.334 mmol) was dissolved in a mixture of THF (3 mL) and DMF (1 mL). Piperidine (0.57 g, 6.68 mmol) was added. The mixture was shaken at room temperature in a Teflon septum capped vial for 20 minutes. TLC indicated complete de-protection at this point. The mixture was concentrated to give an oil. Purification by flash chromatography using a gradient of hexane and EtOAc (5–100% EtOAc in hexane for 25 minutes followed by 100% EtOAc for 5 minutes) gave the desired product (76) upon concentration (0.060 g, 0.170 mmol, 51% yield). LC-MS (ESI): (exact mass: 352.12) m/e=353.3 [M+1]+ (100%), 705.3 [2M+1]+ (5%).

Workup

  1. customcapped vial for 20 minutes
  2. concentrationThe mixture was concentrated
  3. customto give an oil
  4. customPurification by flash chromatography
  5. customa gradient of hexane and EtOAc (5–100% EtOAc in hexane for 25 minutes followed by 100% EtOAc for 5 minutes)

Sources & evidence

ORD record
ord-fd2d6eb5c10749feada7ef07a9d4fc25
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

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