2,2,2-Trifluoroethyl Acetate → HCID 21094402, compound

HRID 1350171Notes

Reaction equation

HRID 1350171 reaction equation
[CH3:1][C:2]([CH3:26])([CH3:25])[C:3]([NH:5][C:6]1[CH:24]=[CH:23][C:9]2[N:10]([CH2:18][C:19]([F:22])([F:21])[F:20])[CH:11]([C:14]([F:17])([F:16])[F:15])[CH2:12][O:13][C:8]=2[CH:7]=1)=[O:4].C([Li])(C)(C)C.C([O:35][CH2:36][C:37]([F:40])([F:39])[F:38])(=O)C>C(OCC)C>[F:38][C:37]([F:40])([F:39])[C:36]([C:7]1[C:8]2[O:13][CH2:12][CH:11]([C:14]([F:17])([F:15])[F:16])[N:10]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:9]=2[CH:23]=[CH:24][C:6]=1[NH:5][C:3](=[O:4])[C:2]([CH3:26])([CH3:25])[CH3:1])=[O:35]

Participants

5

Reactant 3

HCID 1362562,2,2-Trifluoroethyl AcetateHCID 21094395HCID 21094395, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 21094402HCID 21094402, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of (±)-7-(2,2-dimethylpropionamido)-3,4-dihydro-4-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)-2H-1,4-benzoxazine (200 mg, 0.52 mmol) in 3 mL of dry diethyl ether at −30° C. was added t-butyllithium (1.7M/pentane, 0.80 mL, 1.35 mmol) was added dropwise over of 30 min and then stirred at −10° C. The deep yellow solution was allowed to stir at −10° C. for 5–6 hours and then recooled to −30° C. and trifluoroethyl acetate (0.186 mL, 1.56 mmol) was slowly added. The reaction was allowed to gradually warm to room temperature over the course of 12 hours. The reaction was quenched with saturated ammonium chloride (2 mL) and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (5 mL), dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure to give a brown oil. The substrate was purified via flash chromatography (4:1 hexanes:EtOAc) to afford 40 mg (15%) of (±)-3,4-dihydro-8-(trifluoroacetyl)-4-(2,2,2-trifluoroethyl)-3-(trifluoromethyl)-7-(trimethylacetamido)-2H-1,4-benzoxazine. 1H NMR (400 MHz, CDCl3) d 8.92 (s, 1H), 7.81 (d, 1H), 7.06 (d, 1H), 4.68 (d, 1H, J=12), 4.22–4.38 (m, 1H), 4.05–4.12 (m, 1H), 3.93–4.20 (m, 1H), 3.78–3.91 (m, 1H), 1.28 (s, 9H).

Workup

  1. additionwas added dropwise over of 30 min
  2. stirringto stir at −10° C. for 5–6 hours
  3. customrecooled to −30° C.
  4. temperatureto gradually warm to room temperature over the course of 12 hours
  5. customThe reaction was quenched with saturated ammonium chloride (2 mL)
  6. extractionextracted with ethyl acetate (2×10 mL)
  7. washThe combined organic layers were washed with brine (5 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customto give a brown oil
  12. customThe substrate was purified via flash chromatography (4:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-e17de02f8b74475abe25f3b93d0f55a7
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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