Tetrahydrofuran → HCID 86732209, compound

HRID 930380Notes

Reaction equation

HRID 930380 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@:8]2([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[N-:21]=[N+]=[N-].[Na+].C(O)[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].[Na+].CP(C)C.O1CCCC1>[Cu]I.O>[NH2:21][C:2]1[CH:3]=[C:4]([C@:8]2([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 33557Sodium AzideHCID 68983TrimethylphosphineHCID 23667548Sodium AscorbateHCID 86732207HCID 86732207, compound

Product 1

HCID 86732209HCID 86732209, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (4S,6S)-4-(3-bromophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.480 g, 1.352 mmol), sodium azide (0.142 ml, 4.05 mmol), copper(I) iodide (9.16 μl, 11, 0.270 mmol) and L(+)-ascorbic acid sodium salt (0.027 g, 0.135 mmol) was purged with N2 followed by the addition of (1R,2R)-(−)-N,N″-dimethylcyclohexane-1,2-diamine (0.064 ml, 0.405 mmol) and degassed EtOH/water (3/1.5 mL). The resulting mixture was heated at 90° C. for 30 min, then cooled to room temperature, and poured into a mixture of 9:1 saturated NH4Cl solution/NH4OH. The resulting mixture was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, filtered and concentrated. This product was dissolved in a mixture of THF/water (3/1.5 mL) followed by the addition of trimethylphosphine, 1.0M solution in tetrahydrofuran (1.622 ml, 1.622 mmol) and stirred at room temperature for 30 min. The mixture was worked up with water and extracted with dichloromethane three times. The combined organic layers were dried on sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using 5-10% MeOH/dichloromethane to give (4S,6S)-4-(3-aminophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.322 g, 82% yield). MS m/z=292.0 [M+H]+. Calculated for C12H13F4N3O: 291.2

Workup

  1. customwas purged with N2
  2. customdegassed EtOH/water (3/1.5 mL)
  3. temperaturecooled to room temperature
  4. additionpoured into a mixture of 9:1 saturated NH4Cl solution/NH4OH
  5. extractionThe resulting mixture was extracted with EtOAc three times
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThis product was dissolved in a mixture of THF/water (3/1.5 mL)
  10. extractionextracted with dichloromethane three times
  11. customThe combined organic layers were dried on sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-f00b6c55d12d44d5987f06863175ed0c
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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