Tetrahydrofuran → HCID 137331258, compound

HRID 217167Notes

Reaction equation

HRID 217167 reaction equation
[CH3:1][O:2][C:3]([C:5]1[O:13][C:12]2[CH:11]=[CH:10][N:9]=[C:8]([CH2:14][OH:15])[C:7]=2[CH:6]=1)=[O:4].C[C:17]([Si:20](Cl)(C)C)(C)C.[CH3:24]CN(CC)CC.[CH2:31]1[CH2:35]OC[CH2:32]1>CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[O:13][C:12]2[CH:11]=[CH:10][N:9]=[C:8]([CH:14]([C:31]([CH3:32])([CH3:35])[CH3:24])[O:15][SiH2:20][CH3:17])[C:7]=2[CH:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 68940055Methyl 4-(hydroxymethyl)furo[3,2-c]pyridine-2-carboxylate

Product 1

HCID 137331258HCID 137331258, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

(COCl)2 (2.5 mL) was added dropwise to a stirred suspension of furo[3,2-c]pyridine-2-carboxylic acid (1.64 g, 10.1 mmol) in anhydrous CH2Cl2 (40 mL). After effervescence had ceased, the mixture was concentrated. Further CH2Cl2 (20 mL) was added, followed by NEt3 (4 mL) and MeOH (20 mL). After 1 h stirring, the mixture was diluted with EtOAc (50 mL) and washed with H2O, saturated aqueous NaHCO3 and brine. The CH2Cl2 solution was dried (MgSO4), filtered, and concentrated to afford furo[3,2-c]pyridine-2-carboxylic acid methyl ester: δH(CDCl3): 3.96 (s, 3H), 7.48 (d, 1H), 7.54 (s, 1H), 8.59 (d, 1H), 9.00 (s, 1H). A solution of this compound (1.10 g, 6.2 mmol) in MeOH was treated with TFA (0.5 mL). The flask was purged with argon, Bz2O2 (1.50 g, 6.2 mmol) added, and the mixture heated to reflux for 8 h. The mixture was cooled, adsorbed onto silica and purified via column chromatography to furnish 4-hydroxymethylfuro[3,2-c]pyridine-2-carboxylic acid methyl ester: m/z (ES+)=208.0 [M+H]+. A solution of this alcohol (0.50 g, 2.4 mmol), tBDMS-Cl (0.47 g, 3.1 mmol), NEt3 (0.5 mL, 3.6 mmol) and DMAP (catalytic) was stirred in THF overnight. The solution was diluted with EtOAc and washed with H2O and brine, before being dried and concentrated. Purification via chromatography afforded 4-(tert-butylmethylsilanyloxymethyl)furo[3,2-c]pyridine-2-carboxylic acid methyl ester: δH (CDCl3) 0.01 (s, 6H), 0.82 (s, 9H), 3.86 (s, 3H), 4.99 (s, 2H), 7.28 (d, 1H), 7.87 (s, 1H), 8.38 (d, 1H). To a solution of 4-(N-hydroxycarbamimidoylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester (Preparation 9, 93 mg, 340 μmol) in THF was added NaH (60% dispersion in mineral oil, 14 mg, 350 μmol). After effervescence had ceased, 4-(tert-butylmethylsilanyloxymethyl)furo[3,2-c]pyridine-2-carboxylic acid methyl ester (100 mg, 311 μmol) was added. After 3 h at 20° C., the reaction was heated to reflux for 50 min. The mixture was cooled, diluted with EtOAc, washed with saturated aqueous NH4Cl, and brine, before being dried and concentrated. Purification via column chromatography afforded the title compound: m/z (ES+)=545.1 [M+H]+.

Workup

  1. washwashed with H2O and brine
  2. custombefore being dried
  3. concentrationconcentrated
  4. customPurification via chromatography

Sources & evidence

ORD record
ord-cdb147edd1de4e46ae9f68058b2e0106
Source dataset
uspto-grants-2012_06
Patent number
US08193359B2

Reaction notes

Loading…