Trifluoroacetic acid → HCID 71009133, compound

HRID 1626158Notes

Reaction equation

HRID 1626158 reaction equation
C(OC(=O)[NH:7][C:8]1[O:9][CH2:10][C:11]([F:33])([F:32])[C@:12]([C@H:15]2[CH2:17][C@@H:16]2[C:18](=[O:31])[NH:19][C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:29]=2[N:28]=[CH:27][C:26]([Cl:30])=[CH:25]3)([CH3:14])[N:13]=1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Cl:30][C:26]1[CH:27]=[N:28][C:29]2[C:24]([CH:25]=1)=[CH:23][CH:22]=[CH:21][C:20]=2[NH:19][C:18]([C@H:16]1[CH2:17][C@@H:15]1[C@:12]1([CH3:14])[C:11]([F:32])([F:33])[CH2:10][O:9][C:8]([NH2:7])=[N:13]1)=[O:31]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 71008670HCID 71008670, compound

Product 1

HCID 71009133HCID 71009133, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of {(R)-4-[(1S,2S)-rel-2-(3-chloro-quinolin-8-ylcarbamoyl)-cyclopropyl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-carbamic acid tert-butyl ester (4.7 mg, 9.5 μmol) (intermediate J8.2) in dichloromethane (47 μl) was cooled to 0° C. Trifluoroacetic acid (11.0 mg, 7.4 μl, 95.0 μmol) was added and the solution was left to warm to room temperature. After 7 hours trifluoroacetic acid (33.1 mg, 22.3 μl, 285 μmol) was added again and the mixture stirred at room temperature for another hour. Thereafter, the solvent was removed at reduced pressure. The residue was dissolved in water, then the aqueous layer was basified with a solution of sodium carbonate (2M) and extracted 3 times with dichloromethane. The combined extracts were dried over sodium sulphate and evaporated. The (1S,2S)-rel-2-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-cyclopropanecarboxylic acid (3-chloro-quinolin-8-yl)-amide (3.7 mg, 99%) was obtained as a light brown solid. MS (ISP): m/z=395.0 [M+H]+.

Workup

  1. waitthe solution was left
  2. customThereafter, the solvent was removed at reduced pressure
  3. dissolutionThe residue was dissolved in water
  4. extractionextracted 3 times with dichloromethane
  5. dry with materialThe combined extracts were dried over sodium sulphate
  6. customevaporated

Sources & evidence

ORD record
ord-cecc222f9da14b4bb4b5696797519c65
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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