Triethylsilane → HCID 16659482, compound

HRID 990956Notes

Reaction equation

HRID 990956 reaction equation
FC1C=C([N+]([O-])=O)C=CC=1N(CC(F)(F)F)O.CC(C)CCO.[F:24][C:25]1[CH:30]=[C:29]([N+:31]([O-:33])=[O:32])[CH:28]=[CH:27][C:26]=1[N:34]1[C@H:38]([CH:39]([CH3:41])[CH3:40])[CH2:37][O:36][CH:35]1[C:42]([F:45])([F:44])[F:43].[SiH](CC)(CC)CC.[OH-].[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl.O>[F:24][C:25]1[CH:30]=[C:29]([N+:31]([O-:33])=[O:32])[CH:28]=[CH:27][C:26]=1[N:34]([CH2:35][C:42]([F:45])([F:44])[F:43])[C@H:38]([CH:39]([CH3:40])[CH3:41])[CH2:37][OH:36]

Participants

9

Reactant 4

HCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 16659480HCID 16659480, compoundHCID 86758557HCID 86758557, compound

Product 1

HCID 16659482HCID 16659482, compoundYield 88.1%

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(2R)-2-[2-Fluoro-4-nitro(2,2,2-trifluoroethyl)anilinol-3-methyl-1-butanol (Structure 38 of Scheme VIII, where R4=isopropyl, Rx=CF3. To a solution of (4R)-3-(2-fluoro-4-nitrophenyl)-4-isopropyl-2-trifluoromethyloxazolidine (1.8 g, 5.6 mmol) and Et3SiH (1.88 g, 16.1 mmol) in 15 mL CHCl3 was added TiCl4 (6 mL of a 1M solution in CH2Cl2, 6 mmol) at −78° C. The solution was stirred for 2 h, then allowed to warm to 0° C. and stirred for 2 h. The mixture was poured into 150 mL water and neutralized with 6N NaOH. The aqueous layer was extracted with CHCl3 (3×100 mL), and the combined organic layers washed with brine (150 mL), dried over MgSO4, filtered and concentrated. Flash chromatography (gradient elution, hexanes:EtOAc 9:1 to 3:1) afforded 1.6 g (88%) of (2R)-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)anilino]-3-methyl-1-butanol, an orange oil. Data for (2R)-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)anilino]-3-methyl-1-butanol: Rf 0.3 (3:1 hexanes:EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.96 (dd, 1H, J=8.8, 2.3), 7.92 (dd, 1H, J=13.4, 2.5), 7.37 (dd, 1H, J=8.8, 8.8), 4.33-4.23 (m, 1H), 4.03-3.86 (m, 2H), 3.81-3.74 (m, 1H), 3.36-3,27 (m, 1H), 1.97-1.88 (m, 1H), 1.85 (broad s, 1H), 0.99 (d, 3H, J=6.6), 0.94 (d, 3H, J=6.6).

Workup

  1. stirringstirred for 2 h
  2. extractionThe aqueous layer was extracted with CHCl3 (3×100 mL)
  3. washthe combined organic layers washed with brine (150 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washFlash chromatography (gradient elution, hexanes:EtOAc 9:1 to 3:1)

Sources & evidence

ORD record
ord-2a17417b447a4a63813f7e97b4c247e3
Source dataset
uspto-grants-2002_10
Patent number
US06462038B1

Reaction notes

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