Lithium Hexamethyldisilazide → HCID 89704860, compound

HRID 929007Notes

Reaction equation

HRID 929007 reaction equation
[CH:1]([O:3][CH2:4][CH2:5][O:6][NH2:7])=[CH2:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:18][C:19]1[C:24]2[N:25]=[CH:26][S:27][C:23]=2[CH:22]=[C:21]([C:28](OC)=[O:29])[C:20]=1[NH:32][C:33]1[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=1[F:40]>C1COCC1>[F:18][C:19]1[C:24]2[N:25]=[CH:26][S:27][C:23]=2[CH:22]=[C:21]([C:28]([NH:7][O:6][CH2:5][CH2:4][O:3][CH:1]=[CH2:2])=[O:29])[C:20]=1[NH:32][C:33]1[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=1[F:40]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 89704810HCID 89704810, compound

Product 1

HCID 89704860HCID 89704860, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of O-(2-(vinyloxy)ethyl)hydroxyl-amine (172 mg, 1.62 mmol) in THF (6 mL) was added LiHMDS (2.5 mL, 1 M in THF, 2.5 mmol) at −78° C. After stirring at this temperature for 10 min, a solution of methyl 4-fluoro-5-((2-fluoro-4-iodophenyl)amino)benzo[d]thiazole-6-carboxylate (360 mg, 0.81 mmol) in THF was syringed dropwisely. Then the mixture was allowed to warm to ambient temperature, quenched with saturated NH4Cl (aq., 20 mL) and extracted with ethyl acetate (15 mL×3). The combined organic extract was washed with water (10 mL×3) and brine (10 mL), dried over Na2SO4, filtered and concentrated in vacuo. After purification by flash chromatography (petroleum ether/ethyl acetate, 10:1, v/v), the desired product was obtained (410 mg, 98% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.85 (s, 1H), 8.98 (s, 1H), 8.04 (s, 1H), 7.89 (s, 1H), 7.55 (d, J=10.8 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 6.53 (dd, J=13.9, 6.6 Hz, 1H), 6.42 (d, J=6.0 Hz, 1H), 4.21 (d, J=14.5 Hz, 1H), 4.01 (m, 3H), 3.83 (m, 2H).

Workup

  1. customquenched with saturated NH4Cl (aq., 20 mL)
  2. extractionextracted with ethyl acetate (15 mL×3)
  3. extractionThe combined organic extract
  4. washwas washed with water (10 mL×3) and brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customAfter purification by flash chromatography (petroleum ether/ethyl acetate, 10:1

Sources & evidence

ORD record
ord-a24ddcfb1d2249be9d1bb754a2ebcd75
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

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