Water → HCID 70251352, compound

HRID 2205470Notes

Reaction equation

HRID 2205470 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([NH:10][S:11](/[CH:14]=[CH:15]/[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)(=[O:13])=[O:12])[CH:7]=[CH:8][CH:9]=1.[Cl:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Br.O>C1COCC1>[Cl:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27][N:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([Cl:3])[CH:5]=1)[S:11](/[CH:14]=[CH:15]/[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=1)(=[O:13])=[O:12]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 89442503HCID 89442503, compound

Product 1

HCID 70251352HCID 70251352, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a well-stirred suspension of NaH (23.2 mg, 0.92 mmol, 5.6 eq.) in 4 mL of THF, a THF solution (1.5 mL) of compound 2 (53.9 mg, 0.16 mmol, 1 eq.) was added and the mixture was stirred for 1 hour at room temperature. Afterwards, the reaction mixture was cooled at 0° C. and a THF solution (1.5 mL) of 3-chlorobenzylbromide (52.2 mg, 0.25 mmol, 1.5 eq.) was added. After the reaction mixture was stirred at room temperature for 22 h, water was added and the product was extracted three times from the aqueous phase with EtOAc. The resulting organic phase was washed with brine, dried under Na2SO4 and the solvent evaporated. After the product was purified from the crude by flash column chromatography (15% EtOAc/hexanes), compound ef-rs-03-075 (26.1 mg, 0.06 mmol) was obtained in a 35% yield. 1H NMR (400 MHz, CDCl3) δ 7.46 (s, ArH, 1H), 7.42 (dt, J=7.6, 1.7 Hz, ArH, 1H), 7.36 (m, ArH, 3H), 7.23 (m, ArH, 6H), 7.14 (m, ArH, 2H), 6.78 (d, J=15.4 Hz, C═CH, 1H), 4.76 (s, CH2, 2H). 13C NMR (100 MHz, CDCl3, δ): 141.55 (CH), 140.00 (C), 137.62 (C), 135.26 (C), 134.81 (C), 134.51 (C), 134.14 (C), 131.04 (CH), 130.45 (CH), 130.24 (CH), 129.92 (CH), 128.91 (CH), 128.56 (CH), 128.49 (CH), 128.27 (CH), 127.97 (CH), 127.03 (CH), 126.59 (CH), 126.55 (CH), 124.48 (CH), 54.36 (CH2).

Workup

  1. temperatureAfterwards, the reaction mixture was cooled at 0° C.
  2. stirringAfter the reaction mixture was stirred at room temperature for 22 h
  3. extractionthe product was extracted three times from the aqueous phase with EtOAc
  4. washThe resulting organic phase was washed with brine
  5. customdried under Na2SO4
  6. customthe solvent evaporated
  7. customAfter the product was purified from the crude by flash column chromatography (15% EtOAc/hexanes)
  8. customcompound ef-rs-03-075 (26.1 mg, 0.06 mmol) was obtained in a 35% yield

Sources & evidence

ORD record
ord-9373878ec8fe46d28d9e2aa36f1de7dc
Source dataset
uspto-grants-2016_06
Patent number
US09371307B2

Reaction notes

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