1,2-Dichloroethane → 3-Hydroxybenzamide

HRID 2113735Notes

Reaction equation

HRID 2113735 reaction equation
C[O:2][C:3]1[CH:8]=[C:7]([C:9]([NH:11][C@H]2[C@H](N3C4N=CN=C(NCC5C6C(=CC=CC=6)C=CC=5)C=4N=C3)O[C@H](CO)[C@H]2O)=[O:10])[CH:6]=[C:5](OC)[CH:4]=1.NCC1SC=CC=1.C(O)(=O)C1C(=CC=CC=1)O.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.CCOC(C)=O>[OH:2][C:3]1[CH:8]=[C:7]([CH:6]=[CH:5][CH:4]=1)[C:9]([NH2:11])=[O:10]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 338Salicylic AcidHCID 34005(2-Thienylmethyl)amineHCID 757711-HydroxybenzotriazoleHCID 446186HCID 446186, compound

Product 1

HCID 3424033-HydroxybenzamideYield 73%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the crude NMDBA salt of 18d (3.2 g, “5.1 mmol”), salicylic acid (987 mg, 7.14 mmol), HOBt (966 mg, 7.14 mmol), and EDC (1.37 g, 7.14 mmol) in DMF (69 ml) was stirred for 1 h at 23° C. The mixture was diluted with EtOAc (700 ml) and washed (3×H2O; brine). The aqueous layers were back-extracted with EtOAc (250 ml). The combined organic layers were concentrated and chromatographed (EtOAc:cyclohexane 1:1→2:1) to give 2.18 g (73%) of the title 3-hydroxybenzamide, which was further purified by preparative reverse-phase HPLC(H2O:CH3CN 70:40 →25:75 over 35 min, Rt=31 min) to give 1.50 g (50%) of a white powder: m.p. 174.5-175.5° C. 1H NMR (DMSO-d6) δ10.03 (s, 1H), 9.75-9.65 (br. d, 1H), 9.15 (t, J=6.0 Hz, 1H), 8.33-8.29 (br. s, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.42 (d, J=3.8 Hz, 1H), 7.27-21 (m, 4H), 7.01 (d, J=3.8 Hz, 1H), 6.91 (dt, J=7.1, 2.2 Hz), 4.59 (d, J=5.8 Hz, 2H), 2.69 (q, J=7.0 Hz, 2H), 2.04 (t, J=6.9 Hz, 2H), 1.67 (quint, J=7.1 Hz, 2H). 13C NMR (DMSO-d6) δ169.65, 167.57, 158.49, 154.79, 149.06, 142.54 (q, J=4 Hz, C—C—CF3), 136.39, 132.80, 131.61, 126.91, 124.82, 122.93 (q, J=271 Hz, CF3), 117.66, 116.22, 114.01, 112.91, 112.01 (q, J=33 Hz, C—CF3), 39.19, 36.62, 29.42, 23.35. 19F NMR (DMSO-d6) δ-59.52 (s). M/Z APCI: 592 (M+1), 590 (M−1). Anal. HPLC: Rt=6.22 min (method a). C24H23F3N4O7S3 Calc.: C: 44.63%. H, 3.8%. N, 11.83%. Found: C, 44.68%, H, 3.59%, N: 11.90%.

Workup

  1. washwashed (3×H2O; brine)
  2. extractionThe aqueous layers were back-extracted with EtOAc (250 ml)
  3. concentrationThe combined organic layers were concentrated
  4. customchromatographed (EtOAc:cyclohexane 1:1→2:1)

Sources & evidence

ORD record
ord-d3c3147493c04d03b4abaeab50e276ee
Source dataset
uspto-grants-2008_10
Patent number
US07432286B1

Reaction notes

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