Hydrogen chloride-ethyl acetate → HCID 89544873, compound
Reaction equation
C(OC([NH:8][C@@H:9]([C:12]1[C:13]([F:30])=[C:14]([C:26]([Cl:29])=[CH:27][CH:28]=1)[C:15]([C:17]1[CH:18]=[CH:19][C:20]([C:23]([OH:25])=[O:24])=[N:21][CH:22]=1)=[O:16])[CH2:10][CH3:11])=O)(C)(C)C.Cl.CCOC(C)=O>>[NH2:8][C@@H:9]([C:12]1[C:13]([F:30])=[C:14]([C:26]([Cl:29])=[CH:27][CH:28]=1)[C:15]([C:17]1[CH:18]=[CH:19][C:20]([C:23]([OH:25])=[O:24])=[N:21][CH:22]=1)=[O:16])[CH2:10][CH3:11]Participants
Procedure
To a stirred solution of Intermediate 2 (0.4 g, 1.39 mmol) in THF (10 mL) at −78° C. was added butyllithium solution (2.5 M in hexanes, 1.28 mL, 3.19 mmol) dropwise. The solution was stirred at −78° C. for 1 hour and then a solution of 5-(methoxycarbonyl)pyridine-2-carboxylic acid (0.252 g, 1.39 mmol) in THF (10 mL) pretreated with 60% NaH (0.061 g, 1.59 mmol) for 15 mins was added dropwise. The reaction was stirred at −78° C. for 45 mins, and then quenched by the addition of saturated NH4Cl solution. Water and EtOAc were added and the phases were separated. The organic extract was dried (Na2SO4), filtered and concentrated. Biotage column eluting with a gradient of 0%-50% EtOAc/petrol gave 5-[3-((R)-1-tert-butoxycarbonylamino-propyl)-6-chloro-2-fluoro-benzoyl]-pyridine-2-carboxylic acid (0.06 g), MS: [M+H] 437. 5-[3-((R)-1-tert-Butoxycarbonylamino-propyl)-6-chloro-2-fluoro-benzoyl]-pyridine-2-carboxylic acid (0.06 g, 0.137 mmol) was treated with saturated HCl/EtOAc and stirred at ambient temperature for 1 hour. The resulting solid was filtered off and washed with ether to give 5-[3-((R)-1-amino-propyl)-6-chloro-2-fluoro-benzoyl]-pyridine-2-carboxylic acid (0.03 g).
Workup
- filtrationThe resulting solid was filtered off
- washwashed with ether
Sources & evidence
- ORD record
- ord-df89bd1a9601477aa2f437e6f726a10a
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09145354B2
Reaction notes
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