Ethyl Acetate → HCID 178487869, compound

HRID 633842Notes

Reaction equation

HRID 633842 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[Br-].[Cl:12][C:13]1[CH:14]=[N:15][C:16]2[C:21]([C:22]=1[CH2:23][CH2:24][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[CH:20][C:19]([O:44][CH3:45])=[CH:18][CH:17]=2.[C:46]([O:50][C:51](=[O:61])[NH:52][C@H:53]1[CH2:58][CH2:57][C@H:56]([CH:59]=O)[CH2:55][CH2:54]1)([CH3:49])([CH3:48])[CH3:47].C(OCC)(=O)C>O1CCCC1>[C:46]([O:50][C:51](=[O:61])[NH:52][C@H:53]1[CH2:54][CH2:55][C@H:56]([CH:59]=[CH:24][CH2:23][C:22]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:44][CH3:45])[CH:20]=3)[N:15]=[CH:14][C:13]=2[Cl:12])[CH2:57][CH2:58]1)([CH3:49])([CH3:47])[CH3:48]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86730714HCID 86730714, compoundHCID 178453955HCID 178453955, compound

Product 1

HCID 178487869HCID 178487869, compoundYield 61.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

Sodium hexamethyldisilazide (1.0 M in tetrahydrofuran, 3.27 mL, 3.27 mmol, 2.3 eq) is added dropwise at −78° C. to a stirred solution of [2-(3-chloro-6-methoxy-quinolin-4-yl)-ethyl]-triphenyl-phosphonium bromide (800 g, 1.42 mmol, 1.0 eq) in tetrahydrofuran (25 mL). The reaction mixture is then stirred for 45 minutes at −10° C. before lowering down the temperature to −78° C. followed by the addition of (trans-4-formyl-cyclohexyl)-carbamic acid tert-butyl ester (420 mg, 1.85 mmol, 1.3 eq). The reaction mixture is then stirred at 0° C. for 1 hour, extracted with ethyl acetate (3×30 mL) and a saturated ammonium chloride aqueous solution (30 mL). The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 8:1, v/v) to afford {trans-4-[3-(3-chloro-6-methoxy-quinolin-4-yl)-propenyl]-cyclohexyl}-carbamic acid tert-butyl ester as an off-white solid (374 mg, 61% yield).

Workup

  1. custombefore lowering down the temperature to −78° C.
  2. stirringThe reaction mixture is then stirred at 0° C. for 1 hour
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude product that
  9. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-2f6431445b6b4e21b3ef49c26965b065
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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