Acetic Acid → HCID 86691574, compound

HRID 514162Notes

Reaction equation

HRID 514162 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][S:13]([C:16]([F:19])([F:18])[F:17])(=[O:15])=[O:14])=[C:4]([C@H:20]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:3]=1[CH3:31].C([Li])(C)(C)C.C[Si]([N:41]=[C:42]=[O:43])(C)C.CC(O)=O>C1COCC1.C([O-])(O)=O.[Na+].O.CCO>[C:27]([O:26][C@@H:20]([C:4]1[C:3]([CH3:31])=[C:2]([C:42](=[O:43])[NH2:41])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1[O:12][S:13]([C:16]([F:19])([F:17])[F:18])(=[O:15])=[O:14])[C:21]([O:23][CH2:24][CH3:25])=[O:22])([CH3:29])([CH3:30])[CH3:28]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 70696Trimethylsilyl isocyanateHCID 86691575HCID 86691575, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 86691574HCID 86691574, compoundYield 40.2%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
23 °C

Procedure

A solution of (S)-ethyl 2-(4-bromo-3-methyl-1 (trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-tert-butoxyacetate (200 mg, 0.380 mmol) in dry THF (7.6 mL) was cooled to −78° C. tert-butyllithium (1.7 M in pentane, 446 μL, 0.759 mmol) was added dropwise under N2 over 3 min. 10 min later, trimethylsilylisocyanate (62.0 μL, 0.456 mmol) was quickly added. The reaction was warmed to 23° C. After 1 h, the system was treated with glacial AcOH (87.0 μL, 1.52 mmol) followed by EtOH (absolute, 1.9 mL). The reaction was stirred for 30 min then diluted with saturated NaHCO3 (20 mL) and H2O (10 mL). The system was extracted with DCM (3×15 mL). Combined organic phases were dried (Na2SO4), filtered, and concentrated. The residue was treated with benzene and wet-loaded onto a silica gel column and purified by flash chromatography (ethyl acetate/hexanes) giving the desired product (75 mg, 40% yield.) 1H NMR (400 MHz, CDCl3) δ 8.10-8.05 (m, 1H), 7.96-7.86 (m, 1H), 7.64-7.58 (m, 2H), 6.19 (s, broad, 1H), 6.06 (s, broad, 1H), 5.75 (s, 1H), 4.30-4.07 (m, 2H), 2.53 (s, 3H), 1.21 (s, 9H), 1.20 (t, J=7.0 Hz, 3H). 19F NMR (377 MHz, CDCl3) δ−73.2 (s).

Workup

  1. additionwas added dropwise under N2 over 3 min
  2. extractionThe system was extracted with DCM (3×15 mL)
  3. dry with materialCombined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe residue was treated with benzene and wet-loaded onto a silica gel column
  7. custompurified by flash chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-424a6da6dca9433eaddf1282a585afd3
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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