Water → (S)-2-sulfamoylamino-6-((1-(3-methylbutanoyl)piperidin-3-yl)methoxy)benzonitrile

HRID 2280127Notes

Reaction equation

HRID 2280127 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH2:11][C@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18](=[O:23])[CH2:19][CH:20]([CH3:22])[CH3:21])[CH2:13]2)[C:3]=1[C:4]#[N:5].[S:24](Cl)(=[O:27])(=[O:26])[NH2:25].O>CC(N(C)C)=O>[S:24]([NH:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH2:11][C@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18](=[O:23])[CH2:19][CH:20]([CH3:21])[CH3:22])[CH2:13]2)[C:3]=1[C:4]#[N:5])(=[O:27])(=[O:26])[NH2:25]

Participants

5

Reactant 3

HCID 962Water2×HCID 24499Chlorosulfamic acidHCID 867142782-Amino-6-(((3S)-1-(3-methyl-1-oxobutyl)-3-piperidinyl)methoxy)benzonitrile

Product 1

HCID 86714277(S)-2-sulfamoylamino-6-((1-(3-methylbutanoyl)piperidin-3-yl)methoxy)benzonitrileYield 87%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (S)-2-amino-6-((1-(3-methylbutanoyl)piperidin-3-yl)methoxy)benzonitrile (example 5b, 54.55 g, 172.95 mmol) in DMA (110 mL) cooled to 0° C. in an ice bath was added sulfamoyl chloride (55 g, 476 mmol) in two portions (20 g and 35 g). The reaction mixture was stirred for 30 minutes at 0° C. under N2, then at room temperature for 4 hours. The reaction mixture was poured slowly into rapidly stirred cold water (2 L) to provide a milky solution. An additional 800 mL of water was added in several portions to precipitate the desired product (at this point the milky solution has become clear). The precipitate was collected by decantation of the water and was suspended in ethyl acetate (500 mL) then rapidly stirred until it became a fine white solid. The solid material was collected by vacuum filtration and dried under vacuum to give (S)-2-sulfamoylamino-6-((1-(3-methylbutanoyl)piperidin-3-yl)methoxy)benzonitrile as a white solid (59.25 g, 150.2 mmol) in 87% yield. MS 395 (MH+)

Workup

  1. waitat room temperature for 4 hours
  2. customto provide a milky solution
  3. customto precipitate the desired product (at this point the milky solution
  4. customThe precipitate was collected by decantation of the water
  5. stirringthen rapidly stirred until it
  6. filtrationThe solid material was collected by vacuum filtration
  7. customdried under vacuum

Sources & evidence

ORD record
ord-c6c5753dd21b4011bf6d6f71546d6415
Source dataset
uspto-grants-2015_09
Patent number
US09138013B2

Reaction notes

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