Acrylic Acid → HCID 117607121, compound

HRID 588837Notes

Reaction equation

HRID 588837 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[CH:17]=[C:18]([C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=3[Cl:32])[C:19]([Cl:24])=[CH:20][C:21]=2[O:22][CH3:23])=[O:15])[CH:10]([CH2:33][OH:34])[CH2:9]1)=O)(C)(C)C.[C:35]([OH:39])(=O)[CH:36]=[CH2:37].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>Cl.CO.CN(C=O)C.O>[OH:34][CH2:33][CH:10]1[N:11]([C:14]([C:16]2[CH:17]=[C:18]([C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=3[Cl:32])[C:19]([Cl:24])=[CH:20][C:21]=2[O:22][CH3:23])=[O:15])[CH2:12][CH2:13][N:8]([C:35](=[O:39])[CH:36]=[CH2:37])[CH2:9]1

Participants

9

Reactant 4

HCID 6581Acrylic AcidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 117607173HCID 117607173, compound

Product 1

HCID 117607121HCID 117607121, compoundYield 24.1%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

tert-butyl3-(hydroxymethyl)-4-(2′,5′,6-trichloro-4-methoxy-[1,1′-biphenyl]-3-carbonyl)piperazine-1-carboxylate (420 mg, 0.79 mmol) was stirred in HCl in MeOH (2.85N). The solvent was removed under reduced pressure to yield the crude reside which was dissolved in DMF (20 mL), acrylic acid (57 mg, 0.79 mmol), BOP (421 mg, 0.95 mmol) and DIEA (409 mg, 3.17 mmol) were added. The reaction was stirred at room temperature for 1 h. The resulting mixture was poured into water, extracted with ethyl acetate and washed with water and brine. The combined organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (dichloromethane/methanol=60:1) to afford the desired product (92 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ: 7.64-7.20 (m, 5H), 6.83-6.70 (m, 1H), 6.16-6.11 (d, 1H), 5.74-5.71 (d, 1H), 6.91 (s, 1H), 5.08-4.01 (m, 3H), 3.90-3.86 (d, 3H), 3.49-3.22 (m, 2H), 2.93-2.74 (m, 2H), 2.89-2.67 (m, 2H). ESI-MS m/z: 451.2 [M−H]−.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto yield the crude reside which
  3. extractionextracted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe combined organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (dichloromethane/methanol=60:1)

Sources & evidence

ORD record
ord-f1504ad52854423bb677e4260c7062a1
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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