Hydrochloric Acid → HCID 178521304, compound

HRID 1839965Notes

Reaction equation

HRID 1839965 reaction equation
[F:1][C:2]([F:30])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([CH2:23][CH:24]([OH:29])[C:25]([F:28])([F:27])[F:26])[C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=2)[C:18]#[N:19])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:5])[F:4].C[Sn]([N:35]=[N+:36]=[N-:37])(C)C.C1COCC1.Cl>C1(C)C=CC=CC=1>[F:1][C:2]([F:30])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([C:15]2[CH:22]=[CH:21][CH:20]=[C:17]([C:18]3[NH:37][N:36]=[N:35][N:19]=3)[CH:16]=2)[CH2:23][CH:24]([OH:29])[C:25]([F:27])([F:28])[F:26])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:5])[F:4]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8028TetrahydrofuranHCID 5104973Azido(trimethyl)stannane2×HCID 235060423-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl]-(3,3,3-trifluoro-2-hydroxypropyl)amino]benzonitrile

Product 1

HCID 178521304HCID 178521304, compoundYield 33.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

To a solution of 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3,3,3-trifluoro-2-hydroxypropyl)amino]benzonitrile (76 mg, 0.17 mmol) in 2 mL of toluene was added trimethyltin azide (41 mg, 0.20 mmol). The reaction mixture was heated to 105° C. and stirred overnight. TLC showed starting material to still be present so additional trimethyltin azide (41 mg, 0.20 mmol) was added. The reaction mixture was stirred overnight at 105° C., cooled to room temperature, then THF (800 μL) and concentrated HCl (500 μL) were added. HPLC analysis showed 2 peaks after 5 hours, so additional concentrated HCl (200 μL) was added. After stirring overnight, HPLC analysis showed the reaction to be complete. The mixture was filtered through a celite plug and evaporated in vacuo. The residue was purified by reverse phase HPLC eluting with 10% to 90% acetonitrile in water to give 27.2 mg (33%) of the desired tetrazole product as an oil. HRMS calcd. for C19H16F7N5O2: 480.1270 [M+H]+, found: 480.1252. 1H NMR (CDCl3) δ 3.66-3.99 (m, 2H), 4.45-4.75 (m, 3H), 5.80 (dt, 1H), 6.49-6.70 (m, 1H), 6.95 (s, 1H), 6.97-7.06 (m, 3H), 7.18-7.28 (m, 3H), 7.34 (s, 1H).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred overnight at 105° C.
  3. temperaturecooled to room temperature
  4. customafter 5 hours
  5. stirringAfter stirring overnight
  6. customthe reaction
  7. filtrationThe mixture was filtered through a celite plug
  8. customevaporated in vacuo
  9. customThe residue was purified by reverse phase HPLC
  10. washeluting with 10% to 90% acetonitrile in water

Sources & evidence

ORD record
ord-23193feebb9648c396e2a48e82beba71
Source dataset
uspto-grants-2004_01
Patent number
US06677382B1

Reaction notes

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