Hydrochloric Acid → (1R)-1-{4-chloro-2-fluoro-3-[(pyridin-3-yl)carbonyl]phenyl}propan-1-amine

HRID 2283393Notes

Reaction equation

HRID 2283393 reaction equation
C(OC(=O)[NH:7][C@@H:8]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([C:18]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)=[O:19])[C:12]=1[F:26])[CH2:9][CH3:10])(C)(C)C.Cl.O1CCOCC1>C(Cl)Cl>[NH2:7][C@@H:8]([C:11]1[C:12]([F:26])=[C:13]([C:18]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)=[O:19])[C:14]([Cl:17])=[CH:15][CH:16]=1)[CH2:9][CH3:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 89545035{(R)-1-[4-chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propyl}-carbamic acid tert-butyl ester

Product 1

HCID 89544767(1R)-1-{4-chloro-2-fluoro-3-[(pyridin-3-yl)carbonyl]phenyl}propan-1-amineYield 125.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Step 2 To a solution of {(R)-1-[4-chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propyl}-carbamic acid tert-butyl ester (16.0 g, 40.7 mmol) in DCM (300 mL) was added 4M HCl in dioxane (41 mL, 162 mmol, 4 eq) and the reaction stirred for 18 h. The mixture was concentrated and then triturated with diethyl ether (˜200 mL) and the pale green solid filtered off and dried in a vacuum oven to give [3-((R)-1-Amino-propyl)-6-chloro-2-fluoro-phenyl]-pyridin-3-yl-methanone (15.0 g) as the HCl salt. Material contains about 1.3 g dioxane (from NMR ratio), which was not removed from vacuum oven drying.

Workup

  1. concentrationThe mixture was concentrated
  2. customtriturated with diethyl ether (˜200 mL)
  3. filtrationthe pale green solid filtered off
  4. customdried in a vacuum oven

Sources & evidence

ORD record
ord-44e08cbd93c24d268d2287e9b034cb15
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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