Hexane → HCID 68173881, compound

HRID 707690Notes

Reaction equation

HRID 707690 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[F:19].[F:20][CH2:21][C@@H:22]([O:25][CH2:26][C:27](N(OC)C)=[O:28])[CH:23]=[CH2:24].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[F:20][CH2:21][C@@H:22]([O:25][CH2:26][C:27]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[F:19])=[O:28])[CH:23]=[CH2:24]

Participants

8

Reactant 5

HCID 8058HexaneHCID 25517Ammonium ChlorideHCID 612591-Bromo-2-fluorobenzeneHCID 86724401HCID 86724401, compoundHCID 178418339Butyllithium

Product 1

HCID 68173881HCID 68173881, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyllithium in hexane (2.50 M; 176.52 mL, 441.29 mmol) was added dropwise over 20 mins to a solution of 2-bromofluorobenzene (49.00 mL, 451.88 mmol) in THF (670 mL) under a N2 atmosphere at −78° C. The temperature of the reaction was kept below −60° C. during the addition. The yellow solution was stirred at −78° C. for 30 mins. (S)-2-((1-fluorobut-3-en-2-yl)oxy)-N-methoxy-N-methylacetamide (67.50 g, 353.03 mmol) was added dropwise as a solution in THF (100 mL) keeping the internal temperature below −60° C. The reaction was stirred at −78° C. for 45 mins. Aqueous NH4Cl (200 mL) was added to the reaction solution and was allowed to warm up to RT and EtOAc (700 mL) was added. The two layers were separated. The aqueous layer was extracted with EtOAc (300 mL). The combined organic portions were washed with water 9300 mL), dried over MgSO4, (40 g) and concentrated. The crude product was purified by silica gel column chromatography (1% to 10% EtOAc in hexanes) to obtain the title compound as a yellow liquid (63.78 g, 80%). 1H-NMR (400 MHz, CDCl3) δ ppm 4.16-4.31 (m, 1H) 4.42-4.51 (m, 1H) 4.54-4.61 (m, 1H) 4.67-4.88 (m, 2H) 5.35-5.52 (m, 2H) 5.80 (ddd, J=17.43, 10.29, 7.26 Hz, 1H) 7.11-7.19 (m, 1H) 7.24-7.31 (m, 1H) 7.49-7.60 (m, 1H) 7.92-8.00 (m, 1H).

Workup

  1. additionThe temperature of the reaction was kept below −60° C. during the addition
  2. customthe internal temperature below −60° C
  3. stirringThe reaction was stirred at −78° C. for 45 mins
  4. temperatureto warm up to RT
  5. customThe two layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (300 mL)
  7. washThe combined organic portions were washed with water 9300 mL),
  8. dry with materialdried over MgSO4, (40 g)
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel column chromatography (1% to 10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-58c0215ac22c42fcb808a3e08343ec24
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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