Tetrahydrofuran → N-(3-methylpent-1-yn-3-yl)-4-acetamido-3-nitrobenzamide

HRID 583135

Reaction equation

HRID 583135 reaction equation
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15])(=[O:3])[CH3:2].O1CCCC1.CS(Cl)(=O)=O.Cl.[NH2:28][C:29]([CH3:34])([CH2:32][CH3:33])[C:30]#[CH:31]>C(OCC)(=O)C.O.C(N(CC)CC)C>[CH3:34][C:29]([NH:28][C:9](=[O:11])[C:8]1[CH:12]=[CH:13][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[C:6]([N+:14]([O-:16])=[O:15])[CH:7]=1)([CH2:32][CH3:33])[C:30]#[CH:31]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 31297Methanesulfonyl chlorideHCID 737584-Acetamido-3-nitrobenzoic acidHCID 122329903-Methyl-1-pentyn-3-amine hydrochloride

Product 1

HCID 17760175N-(3-methylpent-1-yn-3-yl)-4-acetamido-3-nitrobenzamideYield 60.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

In a 1000 mL, three-necked, round-bottomed flask fitted with a mechanical stirrer, nitrogen inlet and thermometer were placed 10 g of 4-acetamido-3-nitrobenzoic acid, 200 mL of tetrahydrofuran and 31 mL of triethylamine. The resulting well-stirred mixture was cooled to -30° C. and 3.9 mL of methane sulfonyl chloride were added dropwise while keeping the reaction temperature at -30° C. The resulting suspension was stirred at -30° C. for 30 minutes, after which 6.7 g of 3-amino-3-methyl-1-pentyne hydrochloride were added slowly over a 20 minute period. After the addition was complete, the reaction mixture was stirred at -30° C. for an additional 30 minutes. The reaction mixture was then poured into a mixture of 400 mL water and 200 mL of ethyl acetate. The phases were separated and the aqueous layer was then extracted with ethyl acetate (2×150 mL). The combined organic phases were washed sequentially with water (1×200 mL), 5% aqueous hydrochloric acid (2×200 mL), water (1×200 mL), 2% aqueous sodium hydroxide (2×200 mL) and water (1×200 mL) and then dried over anhydrous magnesium sulfate. The solvent was removed in the rotary evaporator, yielding 8.2 g of N-(3-methylpent-1-yn-3-yl)-4-acetamido-3-nitrobenzamide.

Workup

  1. customIn a 1000 mL, three-necked, round-bottomed flask fitted with a mechanical stirrer, nitrogen inlet
  2. customat -30° C
  3. stirringThe resulting suspension was stirred at -30° C. for 30 minutes
  4. additionAfter the addition
  5. stirringthe reaction mixture was stirred at -30° C. for an additional 30 minutes
  6. customThe phases were separated
  7. extractionthe aqueous layer was then extracted with ethyl acetate (2×150 mL)
  8. washThe combined organic phases were washed sequentially with water (1×200 mL), 5% aqueous hydrochloric acid (2×200 mL), water (1×200 mL), 2% aqueous sodium hydroxide (2×200 mL) and water (1×200 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was removed in the rotary evaporator

Sources & evidence

ORD record
ord-b681e01882a84e66bf20d5bded3cb474
Source dataset
uspto-grants-1999_07
Patent number
US05929098

Linked notes

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