Sodium hydride → tert-Butyl 4-(2-[(cyclopropylmethyl)(methylsulfonyl)amino]phenyl}piperidine-carboxylate

HRID 489664Notes

Reaction equation

HRID 489664 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)(=[O:4])=[O:3].[H-].[Na+].Br[CH2:28][CH:29]1[CH2:31][CH2:30]1>CN(C=O)C>[CH:29]1([CH2:28][N:5]([S:2]([CH3:1])(=[O:3])=[O:4])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[CH:12]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]2)[CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 22266209tert-Butyl 4-{2-[(methylsulfonyl)amino]phenyl}piperidinecarboxylate

Product 1

HCID 22266227tert-Butyl 4-(2-[(cyclopropylmethyl)(methylsulfonyl)amino]phenyl}piperidine-carboxylateYield 99.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a 100 mL round-bottomed flask was added tert-butyl 4-{2-[(methylsulfonyl)amino]phenyl}piperidine-carboxylate (Example 1 Step d) (1.9 grams, 5.4 mmol) and DMF (Aldrich) (30 mL). The solution was magnetically stirred vigorously at 25° C. under N2 atmosphere and treated in portions with NaH as a 60% dispersion in mineral oil (Aldrich) (150 mg, 6.4 mmol). After gas evolution ceased, (bromomethyl)cyclopropane (Aldrich) (675 μL, 940 mg, 7.0 mmol) was introduced via syringe. The reaction mixture was stirred at 25° C. for 15 h. The reaction was quenched by careful addition of satd NH4Cl (150 mL) and extracted with EtOAc (400 mL). The organic layer was washed with H2O (150 mL), satd NaCl (100 mL), dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound as a yellow foam (2.2 g). MS (ESI, pos. ion) m/z: 409 (M+1); (ESI, neg. ion) m/z: 407 (M−1). Calc'd for C21H32N2O4S: 408.56.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. for 15 h
  2. customThe reaction was quenched by careful addition of satd NH4Cl (150 mL)
  3. extractionextracted with EtOAc (400 mL)
  4. washThe organic layer was washed with H2O (150 mL), satd NaCl (100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3acd57f2c5344b38880cd6a77d4dfeef
Source dataset
uspto-grants-2005_12
Patent number
US06977264B2

Reaction notes

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