Acetic Acid → HCID 68530554, compound

HRID 2180190Notes

Reaction equation

HRID 2180190 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:27])[N:11]([CH2:13][C:14]2([C:20]3[CH:25]=[CH:24][C:23]([I:26])=[CH:22][CH:21]=3)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH3:12])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH:28]1([CH:31]=O)[CH2:30][CH2:29]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)CCl.CCOC(C)=O>[CH:28]1([CH2:31][N:17]2[CH2:18][CH2:19][C:14]([CH2:13][N:11]([CH3:12])[C:10]([NH:9][C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)=[O:27])([C:20]3[CH:21]=[CH:22][C:23]([I:26])=[CH:24][CH:25]=3)[CH2:15][CH2:16]2)[CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 224903673-(3,5-Dichloro-phenyl)-1-[4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-1-methyl-urea

Product 1

HCID 68530554HCID 68530554, compoundYield 96.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(3,5-dichloro-phenyl)-1-[4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-1-methyl-urea (˜0.10 g, 0.17 mmol) in ClCH2CH2Cl (1 mL) was added cyclopropanecarboxaldehyde (0.016 mL, 0.204 mmol, 1.2 eq.). The mixture was stirred at room temperature for 15 min and then HOAc (0.01 mL, 1% v/v) was added. The reaction was stirred for a further 1 h. Na(OAc)3BH (0.054 g, 0.255 mmol, 1.5 eq.) was added and the reaction was stirred at room temperature for 12 h. It was diluted with EtOAc (10 mL) and washed with saturated NaHCO3 (10 mL) and saturated brine (10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation to give 1-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-3-(3,5-dichloro-phenyl)-1-methyl-urea (0.094 g, 95%). Crude 1H NMR (CDCl3): δ 7.83 (d, 2H), 7.22 (m, 4H), 7.05 (s, 1H), 6.01 (br.s, 1H), 3.50 (s, 2H), 2.97 (d, 2H), 2.83 (s, 3H), 2.36 (m, 2H), 2.27 (m, 2H), 2.09 (m, 2H), 0.91 (br.m, 1H), 0.58 (d, 2H), 0.15 (d, 2H).

Workup

  1. stirringThe reaction was stirred for a further 1 h
  2. stirringthe reaction was stirred at room temperature for 12 h
  3. washwashed with saturated NaHCO3 (10 mL) and saturated brine (10 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-01db5e57f6f04d28a2d7cf3780e005f7
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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