Pyridine → HCID 86586510, compound

HRID 1350170Notes

Reaction equation

HRID 1350170 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]2[N:6]([CH2:14][C:15]([F:18])([F:17])[F:16])[CH:7]([C:10]([F:13])([F:12])[F:11])[CH2:8][O:9][C:4]=2[CH:3]=1.[CH3:21][C:22]([CH3:27])([CH3:26])[C:23](Cl)=O.N1C=CC=CC=1.C[CH2:35][O:36]C(C)=O>>[F:16][C:15]([F:18])([F:17])[CH2:14][N:6]1[C:5]2[CH:19]=[CH:20][C:2]([NH:1][C:35](=[O:36])[CH2:23][C:22]([CH3:27])([CH3:26])[CH3:21])=[CH:3][C:4]=2[O:9][CH2:8][CH:7]1[C:10]([F:11])([F:12])[F:13]

Participants

5

Reactant 4

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 62493Pivaloyl chlorideHCID 18416175HCID 18416175, compound

Product 1

HCID 86586510HCID 86586510, compoundYield 89%

Procedure

To a solution of (±)-7-amino-3,4-dihydro-4-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)-2H-1,4-benzoxazine (140 mg, 0.47 mmol) in 5 mL EtOAc was added trimethylacetyl chloride (0.085 mL, 0.70 mmol) and anhydrous pyridine (0.056 mL, 0.70 mmol). The solution was allowed to stir at rt for 12 h. The solution was then washed sequentially with saturated sodium bisulfate (2×10 mL), copper sulfate (10 mL) and brine (10 mL). The organic phase was dried with anhydrous magnesium sulfate, filtered and the solvent was evaporated under reduced pressure to yield an oil. The oil was purified via flash chromatography (7:3 hexanes:EtOAc) to afford 160 mg (89%) of (±)-3,4-dihydro-4-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)-7-(trimethylpropionamido)-2H-1,4-benzoxazine. 1H NMR (CDCl3, 400 MHz) d 1.25 (s, 9H), 3.78 (sext, J=8.0 Hz, 1H), 3.88 (m, 1H), 4.02 (m, 1H), 4.22 (sext. J=8.3 Hz, 1H), 4.59 (d, J=11.6 Hz, 1H), 6.77 (d, J=8.8 Hz, 1H), 7.05 (dd, J=2.4 Hz, 8.8 Hz, 1H), 7.11 (d, J=2.44 Hz, 1H), 7.15 (s, 1H).

Workup

  1. washThe solution was then washed sequentially with saturated sodium bisulfate (2×10 mL), copper sulfate (10 mL) and brine (10 mL)
  2. dry with materialThe organic phase was dried with anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent was evaporated under reduced pressure
  5. customto yield an oil
  6. customThe oil was purified via flash chromatography (7:3 hexanes:EtOAc)

Sources & evidence

ORD record
ord-7fc3fb90ac9a432b9e66c38648ea832d
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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