2-Thiophenecarboxaldehyde, 5-chloro- → HCID 86607167, compound

HRID 602505Notes

Reaction equation

HRID 602505 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:15])[CH:3]=1.[Cl:16][C:17]1[S:21][C:20]([CH:22]=O)=[CH:19][CH:18]=1.C([BH3-])#N.[Na+]>C(O)C.CO.C(O)(=O)C>[Cl:15][C:4]1[CH:3]=[C:2]([NH:1][CH2:22][C:20]2[S:21][C:17]([Cl:16])=[CH:18][CH:19]=2)[CH:7]=[CH:6][C:5]=1[NH:8][C:9](=[O:14])[C:10]([F:11])([F:12])[F:13]

Participants

7

Reactant 3

HCID 817002-Thiophenecarboxaldehyde, 5-chloro-HCID 5003444Sodium cyanoborohydrideHCID 28867605HCID 28867605, compound

Product 1

HCID 86607167HCID 86607167, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 887MethanolSolvent2×

Procedure

A solution of N-(4-Amino-2-chlorophenyl)-2,2,2-trifluoroacetamide (4.567 g, 19.14 mmol) and 5-chloro-thiophene-2-carboxaldehyde (3.97 g, 27.1 mmol) in anhydrous ethanol (50 mL) was heated to reflux for 15 minutes and evaporated in vacuo at 70° C. (0.1 mbar, 30 min). The obtained crude imine as a crystalline solid was dissolved in methanol followed by addition of sodium cyanoborohydride (NaBH3CN) in methanol (50 mL) and acetic acid (9 mL) by portions. The obtained reaction mixture was stirred at room temperature for 60 minutes and evaporated in vacuo to small volume. The concentrated solution was quenched with water and filtered after 30 minutes to give 6.98 g (99% yield) of the title compound as a brown-yellow solid. 1H NMR (DMSO-d6): 4.43 (d, 2H), 6.63 (dd, 1H), 6.77 (d, 1H), 6.79 (t, 1H, NH), 6.94 (d, 1H), 6.97 (d, 1H), 7.10 (d, 1H), 10.85 (br. s, 1H, NHCO). LC/MS (m/z) 367.9 (M+); RT=3.36, (UV, ELSD) 99%, 100%.

Workup

  1. temperatureto reflux for 15 minutes
  2. customevaporated in vacuo at 70° C. (0.1 mbar, 30 min)
  3. customThe obtained crude imine as a crystalline solid
  4. customThe obtained reaction mixture
  5. customevaporated in vacuo to small volume
  6. customThe concentrated solution was quenched with water
  7. filtrationfiltered after 30 minutes

Sources & evidence

ORD record
ord-618df8c13f8043d698bbf998b2f397d6
Source dataset
uspto-grants-2011_03
Patent number
US07906537B2

Reaction notes

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