1,2-Dichloroethane → 3-Hydroxybenzamide

HRID 908546Notes

Reaction equation

HRID 908546 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 fiuther 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), 8.3348.29 (br. s, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.42 (d, J=3.8 Hz, 1H), 727-21 (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-e6866b0444044f528ea7014812ed20ed
Source dataset
uspto-grants-2011_09
Patent number
US08017628B2

Reaction notes

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