1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(4-formylphenyl)acetic Acid

HRID 1529534Notes

Reaction equation

HRID 1529534 reaction equation
C([C:3]1[CH:4]=[C:5]([CH2:9][C:10]([OH:12])=[O:11])[CH:6]=[CH:7][CH:8]=1)=O.C1([CH2:16][O:17]C2C=C([C@@H](O)CC3C(Cl)=C[N+]([O-])=CC=3Cl)C=CC=2OC(F)F)CC1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH:16]([C:8]1[CH:3]=[CH:4][C:5]([CH2:9][C:10]([OH:12])=[O:11])=[CH:6][CH:7]=1)=[O:17]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14980951(3-ForMyl-phenyl)-acetic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 113441872-(4-formylphenyl)acetic AcidYield 79.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(3-formylphenyl)acetic acid (394 mg, 2.4 mmol) in DMF (5 mL) was added (1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethanol (1.0 g, 2.4 mmol) followed by DMAP (147 mg, 1.2 mmol) and EDC.HCl (930 mg, 4.8 mmol). The mixture was allowed to stir a room temperature for 18 hours. The solvent was removed in vacuo and the residue was partitioned between DCM (10 mL) and waturated sodium bicarbonate solution (10 mL). The organic phase was passed through a hydrophobic fit and the solvent was removed in vacuo. The crude material was purified by silica gel column chromatography, eluting with 0-100% EtOAc in DCM, to afford the title compound as an off-white solid (312 mg, 23%). 1H NMR (400 MHz, CDCl3): δ 10.00 (s, 1H), 8.04 (s, 2H), 7.81 (d, J=7.5 Hz, 1H), 7.72 (s, 1H), 7.52-7.42 (m, 2H), 7.13 (d, J=8.1 Hz, 1H), 6.91-6.85 (m, 2H), 6.62 (t, J=75.3 Hz, 1H), 6.05 (dd, J=9.9, 4.4 Hz, 1H), 3.85-3.76 (m, 2H), 3.72-3.59 (m, 2H), 3.49 (dd, J=14.0, 9.9 Hz, 1H), 3.18 (dd, J=14.0, 4.4 Hz, 1H), 1.32-1.19 (m, 1H), 0.70-0.63 (m, 2H), 0.40-0.34 (m, 2H). LCMS (Method 2): [MH+]=566 at 3.54 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between DCM (10 mL)
  3. customthe solvent was removed in vacuo
  4. customThe crude material was purified by silica gel column chromatography
  5. washeluting with 0-100% EtOAc in DCM

Sources & evidence

ORD record
ord-89c45595b24c41c38f6e650aeed174c7
Source dataset
uspto-grants-2015_07
Patent number
US09090606B2

Reaction notes

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