Formaldehyde → ((2-Chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-methylamino)-acetic acid ethyl ester

HRID 2250470Notes

Reaction equation

HRID 2250470 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][NH:6][C:7]1[CH:12]=[C:11]([C:13]2[N:17]=[C:16]([C:18]3[S:19][CH:20]=[CH:21][C:22]=3[Cl:23])[O:15][N:14]=2)[CH:10]=[CH:9][C:8]=1[Cl:24])[CH3:2].C=O.[C:28]([BH3-])#N.[Na+].[OH-].[Na+]>C(O)(=O)C>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][N:6]([C:7]1[CH:12]=[C:11]([C:13]2[N:17]=[C:16]([C:18]3[S:19][CH:20]=[CH:21][C:22]=3[Cl:23])[O:15][N:14]=2)[CH:10]=[CH:9][C:8]=1[Cl:24])[CH3:28])[CH3:2]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 16222810(2-Chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenylamino)-acetic acid ethyl ester

Product 1

HCID 16222813((2-Chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-methylamino)-acetic acid ethyl esterYield 97.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a yellow mixture of (2-chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenylamino)-acetic acid ethyl ester (0.360 g, 0.903 mmol), paraformaldehyde (0.271 g, 9.03 mmol) and glacial acetic acid (4.5 mL) was added sodium cyanoborohydride (0.284 g, 4.51 mmol) in small portions over 5 min. The yellow mixture became a white suspension and was stirred overnight at room temperature. The white suspension was added to a 25% NaOH(aq) solution at 0° C. The aqueous layer was extracted with dichloromethane (50 mL), washed with brine (15 mL), dried over MgSO4, filtered and concentrated in vacuo. The clear oil was purified by flash column chromatography (silica gel, elution with EtOAc:hexanes, 1:5) to yield 0.362 g (96%) of the title compound as a white solid. 1H NMR (CDCl3): 7.94 (d, 1H, J=1.7 Hz), 7.73 (td, 1H, J=8.2, 1.9 and 1.7 Hz), 7.61 (dd, 1H, J=5.5, 5.2, 1.6 and 1.4 Hz), 7.45 (dd, 1H, J=8.5 and 1.4 Hz), 7.13 (dd, 1H, J=5.5, 5.2, 1.6 and 1.4 Hz), 4.18 (q, 2H, J=7.1 Hz), 4.04 (s, 2H), 3.07 (s, 3H), 1.26 (t, 3H, J=7.1 Hz).

Workup

  1. extractionThe aqueous layer was extracted with dichloromethane (50 mL)
  2. washwashed with brine (15 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe clear oil was purified by flash column chromatography (silica gel, elution with EtOAc:hexanes, 1:5)

Sources & evidence

ORD record
ord-9fbae5dfa2854bf0b964b1b619ddbb62
Source dataset
uspto-grants-2008_01
Patent number
US07317029B2

Reaction notes

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