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

HRID 856982Notes

Reaction equation

HRID 856982 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 16222810HCID 16222810, compound

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-316ab9d2364c4ed2be7324e7bc2e8c13
Source dataset
uspto-grants-2006_12
Patent number
US07144876B2

Reaction notes

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