Methanol → HCID 16659481, compound

HRID 990952Notes

Reaction equation

HRID 990952 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[C@H:15]([CH2:16][CH3:17])[CH2:14][O:13][CH:12]1[C:18]([F:21])([F:20])[F:19].[SiH](CC)(CC)CC.CO>C(Cl)(Cl)Cl.O>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:12][C:18]([F:21])([F:20])[F:19])[C@H:15]([CH2:16][CH3:17])[CH2:14][OH:13]

Participants

6

Reactant 3

HCID 887MethanolHCID 12052TriethylsilaneHCID 16659479HCID 16659479, compound

Product 1

HCID 16659481HCID 16659481, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To a solution of (4R)-3-(2-fluoro-4-nitrophenyl)-4-ethyl-2-trifluoromethyloxazolidine (9.2 g, 29.8 mmol) and Et3SiH (19.1 mL, 119 mmol) in 100 mL chloroform was added BF3OEt2 (7.56 mL, 60 mmol). The reaction was heated to reflux for 12 hrs, whereupon additional BF3OEt2 (7.56 mL, 60 mmol) was added, and the mixture heated at reflux for an additional 12 hrs. After cooling, MeOH (5 mL) was added and the reaction was allowed to stir at r.t. for an hour. The reaction was poured in water (250 mL) and extracted with ethyl acetate (3×250 mL). The organic layers were combined, washed sequentially with water (250 mL) and brine (250 mL), dried (MgSO4), filtered, and concentrated under reduced pressure to a brown oil. Flash chromatography (gradient elution, hexanes:ethyl acetate 95:5 to 50:50) afforded 5.4 g (59%) of (2R )-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)anilino]-1-butanol. Data for (2R )-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)anilino]-1-butanol: 1H NMR (500 MHz, CDCl3) δ 7.98 (dd, J=8.8, 2.4, 1H), 7.94 (dd, J=13,2, 2.9, 1H), 7.37 (dd, J=8.8, 8.8, 1H), 4.12 (m, 1H), 3.87 (m, 1H), 3.77 (m, 1H), 3.70 (m, 1H), 3.57 (m, 1H), 1.78 (dd, J=6.8, 4.4, 1H), 1.58 (dq, J=7.8, 2.9, 2H), 0.95 (t, J=7.3, 1H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 12 hrs, whereupon additional BF3OEt2 (7.56 mL, 60 mmol)
  3. additionwas added
  4. temperaturethe mixture heated
  5. temperatureat reflux for an additional 12 hrs
  6. temperatureAfter cooling
  7. extractionextracted with ethyl acetate (3×250 mL)
  8. washwashed sequentially with water (250 mL) and brine (250 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to a brown oil
  12. washFlash chromatography (gradient elution, hexanes:ethyl acetate 95:5 to 50:50)

Sources & evidence

ORD record
ord-d0acabc4ffaa43b0a898e361a30eae4d
Source dataset
uspto-grants-2002_10
Patent number
US06462038B1

Reaction notes

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