Hydrochloric Acid → HCID 71572008, compound

HRID 532197Notes

Reaction equation

HRID 532197 reaction equation
[OH:1][B:2]1[C:6]2[CH:7]=[CH:8][C:9](/[CH:11]=[N:12]/[OH:13])=[CH:10][C:5]=2[C:4]([CH3:15])([CH3:14])[O:3]1.C1C(=O)N(Cl)C(=O)C1.[Cl:24][C:25]1[C:30]([F:31])=[CH:29][C:28]([C:32]([C:34]([F:37])([F:36])[F:35])=[CH2:33])=[CH:27][C:26]=1[F:38].Cl>CN(C=O)C.O>[Cl:24][C:25]1[C:26]([F:38])=[CH:27][C:28]([C:32]2([C:34]([F:37])([F:35])[F:36])[O:13][N:12]=[C:11]([C:9]3[CH:8]=[CH:7][C:6]4[B:2]([OH:1])[O:3][C:4]([CH3:15])([CH3:14])[C:5]=4[CH:10]=3)[CH2:33]2)=[CH:29][C:30]=1[F:31]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 31398ChlorosuccinimideHCID 86685069HCID 86685069, compoundHCID 89572652HCID 89572652, compound

Product 1

HCID 71572008HCID 71572008, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
45 °C

Procedure

To a solution of (E)-1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbaldehyde oxime (200 mg, 0.98 mmol) in DMF (7 mL) at rt was added NCS (157 mg, 1.17 mmol). The reaction mixture was warmed to 45° C., stirred for 2.5 h and cooled to rt. This mixture was added dropwise to a solution of 2-chloro-1,3-difluoro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (237 mg, 0.98 mmol) and TEA (218 mg, 2.16 mmol) in DMF (7 mL) at 0° C. The mixture was stirred at this temperature for 1 h, and then at rt overnight. The mixture was acidified with 3 N HCl to pH of 2, then poured into water and extracted with EA (50 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (PE:EA=2:1) to give the final title compound (150 mg, yield 35%) as white solid. 1H NMR (300 MHz, DMSO-d6): δ 9.24 (s, 1H), 7.82-7.73 (m, 3H), 7.71-7.60 (m, 2H), 4.50 (d, J=18.3 Hz, 1H), 4.44 (d, J=18.3 Hz, 1H), 1.51 (s, 3H), 1.50 (s, 3H) ppm; HPLC purity: 95.5% at 214 nm and 97.8% at 254 nm; MS: m/z=446 (M+1, ESI+).

Workup

  1. temperaturecooled to rt
  2. stirringThe mixture was stirred at this temperature for 1 h
  3. customat rt
  4. customovernight
  5. extractionextracted with EA (50 mL×2)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by prep-TLC (PE:EA=2:1)

Sources & evidence

ORD record
ord-fd300dcc8fca413ebf9aff87f9a98c76
Source dataset
uspto-grants-2014_10
Patent number
US08853186B2

Reaction notes

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