Acetic Acid → 3-chloro-N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-4-fluorobenzenesulfonamide

HRID 2180174Notes

Reaction equation

HRID 2180174 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([NH:12][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)(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[CH:27]1([CH:30]=O)[CH2:29][CH2:28]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)CCl.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([NH:12][CH2:13][C:14]2([C:20]3[CH:21]=[CH:22][C:23]([I:26])=[CH:24][CH:25]=3)[CH2:15][CH2:16][N:17]([CH2:30][CH:27]3[CH2:29][CH2:28]3)[CH2:18][CH2:19]2)(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 224903833-chloro-4-fluoro-N-[4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-benzenesulfonamide

Product 1

HCID 685368553-chloro-N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-4-fluorobenzenesulfonamideYield 100%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 3-chloro-4-fluoro-N-[4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-benzenesulfonamide (0.0321 g, 0.04 mmol) in ClCH2CH2Cl (0.5 mL) at room temperature under Ar was added cyclopropanecarboxaldehyde (0.005 mL, 0.048 mmol, 1.2 eq) and HOAc (0.05 mL, 1%v/v). The mixture was stirred for 0.5 h. Na(OAc)3BH (0.015 g, 0.06 mmol, 1.5 eq) was added and the mixture stirred for 16 h, diluted with EtOAc (20 mL) and washed with saturated aqueous NaHCO3 solution (10 mL) and saturated brine (10 mL). The organic layer was dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, then dried under high vacuum to give 3-chloro-N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-4-fluorobenzenesulfonamide (0.047 g, 0.04 mmol, 95%). MS (ESI): 563.1/565.1 (M+1).

Workup

  1. stirringthe mixture stirred for 16 h
  2. washwashed with saturated aqueous NaHCO3 solution (10 mL) and saturated brine (10 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-c7388ea6e5b644a1b0cd4a68211b514d
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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