Trifluoroacetic acid → (R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamide

HRID 2202267Notes

Reaction equation

HRID 2202267 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([NH:20][C:21]([C@@H:23]2[N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30][C:29]3[N:28]=[C:27]([O:40][CH3:41])[CH:26]=[CH:25][C:24]2=3)=[O:22])[CH:12]=[C:13]([F:19])[C:14]=1[Si:15]([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])O.[Na+]>>[F:19][C:13]1[CH:12]=[C:11]([NH:20][C:21]([C@@H:23]2[NH:32][CH2:31][CH2:30][C:29]3[N:28]=[C:27]([O:40][CH3:41])[CH:26]=[CH:25][C:24]2=3)=[O:22])[CH:10]=[C:9]([F:8])[C:14]=1[Si:15]([CH3:18])([CH3:17])[CH3:16]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium Bicarbonate2×HCID 131735741tert-butyl (R)-5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

Product 1

HCID 131735740(R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamideYield 95.3%

Procedure

Cooled TFA (10.5 mL) was added to tert-butyl (R)-5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (747 mg, 1.52 mmol) at room temperature, and the mixture was stirred at room temperature for 3 min. The reaction mixture was poured into ice and aqueous sodium hydrogencarbonate solution, and the pH of the mixture was adjusted to 8 with aqueous sodium hydrogencarbonate solution. Then, the mixture was extracted with ethyl acetate (×3). The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give (R)—N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamide (567 mg, 1.448 mmol, 95%) as a white solid.

Workup

  1. extractionThen, the mixture was extracted with ethyl acetate (×3)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-82efb785507948668b49795b298ecf91
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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