Sodium Hydroxide → 4'-[(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-ylmethyl)-amino]-biphenyl-2-sulfonic acid tert-butylamide

HRID 2373301Notes

Reaction equation

HRID 2373301 reaction equation
[C:1]([NH:5][S:6]([C:9]1[C:10]([C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)=[CH:11][CH:12]=[CH:13][CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:34][C:35]1([CH3:48])[O:47][C:39]2[C:40]([CH3:46])=[N:41][CH:42]=[C:43]([CH:44]=O)[C:38]=2[CH2:37][O:36]1.[BH4-].[Na+].[OH-].[Na+]>ClCCl.C1(C)C=CC=CC=1>[C:1]([NH:5][S:6]([C:9]1[C:10]([C:15]2[CH:20]=[CH:19][C:18]([NH:21][CH2:44][C:43]3[CH:42]=[N:41][C:40]([CH3:46])=[C:39]4[O:47][C:35]([CH3:48])([CH3:34])[O:36][CH2:37][C:38]=34)=[CH:17][CH:16]=2)=[CH:11][CH:12]=[CH:13][CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 521998p-Toluenesulfonic acid monohydrateHCID 4311764Sodium borohydride2×HCID 10804475N-tert-butyl-4'-aminobiphenyl-2-sulfonamideHCID 156199462,2,8-trimethyl-4H-(1,3)dioxino(4,5-c)pyridine-5-carbaldehyde

Product 1

HCID 598525204'-[(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-ylmethyl)-amino]-biphenyl-2-sulfonic acid tert-butylamideYield 24%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 250 mL three neck flask fitted with a condenser and Dean-Stark apparatus was added 4′-amino-biphenyl-2-sulfonic acid tert-butylamide (1.22 g, 4.0 mmol), p-toluenesulfonic acid monohydrate (152 mg, 0.8 mmol), 2,2,8-trimethyl-4H-[1,3]dioxino [4,5-c]pyridine-5-carbaldehyde (995 mg, 4.8 mmol) and toluene (120 ml). The reaction mixture was stirred at 120° C. under nitrogen atmosphere for 7 hours before concentrating to dryness. The resulting solid was then dissolved in acetic acid (20 mL), cooled to 0° C., followed by a slow addition of sodium borohydride (529 mg, 14 mmol). After the addition of sodium borohydride, dichloromethane (30 mL) was then added to the reaction mixture and stirring was continued at room temperature for an additional 3 hours. Sodium hydroxide (5 N) was added to neutralize the solution, and the reaction mixture was extracted with ethyl acetate, dried over MgSO4, filtered and evaporated. The crude mixture was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (1:1) as eluant, to give 4′-[(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-ylmethyl)-amino]-biphenyl-2-sulfonic acid tert-butylamide (1) (0.457 g, 24% yield) as a colorless solid.

Workup

  1. concentrationbefore concentrating to dryness
  2. dissolutionThe resulting solid was then dissolved in acetic acid (20 mL)
  3. temperaturecooled to 0° C.
  4. additionwas then added to the reaction mixture
  5. stirringstirring
  6. waitwas continued at room temperature for an additional 3 hours
  7. extractionthe reaction mixture was extracted with ethyl acetate
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude mixture was purified by column chromatography on silica gel using
  12. additiona mixture of ethyl acetate and hexane (1:1) as eluant

Sources & evidence

ORD record
ord-e8ebec40eba24944bd79849d82a35b6c
Source dataset
uspto-grants-2008_12
Patent number
US07459468B2

Reaction notes

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