Hydrochloric Acid → 4-amino-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide

HRID 1881028

Reaction equation

HRID 1881028 reaction equation
[F:1][C:2]1[CH:17]=[C:16]([N+:18]([O-])=O)[C:15]([O:21][CH3:22])=[CH:14][C:3]=1[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][N:10]([CH3:13])[CH2:9][CH2:8]1)=[O:5].Cl.[H][H]>CCO.[Pd]>[NH2:18][C:16]1[C:15]([O:21][CH3:22])=[CH:14][C:3]([C:4]([NH:6][CH:7]2[CH2:12][CH2:11][N:10]([CH3:13])[CH2:9][CH2:8]2)=[O:5])=[C:2]([F:1])[CH:17]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 671177462-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)-4-nitrobenzamideHCID 178418361HCID 178418361, compound

Product 1

HCID 669272854-amino-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamideYield 100.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of 2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)-4-nitrobenzamide (55 g, 177 mmol) in EtOH (450 mL) was added 10% Pd/C (11 g), followed by 4.4 mL of concentrated HCl. The reaction mixture was hydrogenated using a hydrogen balloon for 22 h. The solution was filtered through celite and concentrated to a minimum volume, after which solid was filtered, washed with ether. The filtrate concentrated again and trituated with EtOH and repeated several times to get out more products. The solid was combined and further dried to give total 50 g of product as light yellow powder (>98%). 1H NMR (400 MHz, DMSO-d6) δ 1.64-2.02 (m, 4 H) 2.61 (s, 3 H) 2.90 (t, J=11.0 Hz, 2 H) 3.24 (m, 2 H) 3.72-3.81 (m, 3 H) 3.84-4.03 (m, 1 H) 5.60 (s, 2 H) 6.29-6.50 (m, 1 H) 7.01 (d, J=6.8 Hz, 1 H) 7.69 (dd, J=7.3, 4.8 Hz, 1 H). [M+H] calc'd for C14H20FN3O2, 282; found 282.

Workup

  1. customfor 22 h
  2. filtrationThe solution was filtered through celite
  3. concentrationconcentrated to a minimum volume
  4. filtrationafter which solid was filtered
  5. washwashed with ether
  6. concentrationThe filtrate concentrated again
  7. customto get out more products
  8. customfurther dried

Sources & evidence

ORD record
ord-c0dd26107b2c4f47a158901e938aa8f7
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Linked notes

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