Water → N-[4-chloro-2-fluoro-5-(2-propynyloxy)phenyl]-3-azabicyclo-[3.1.0]hexane-2-carboxamide

HRID 1940481Notes

Reaction equation

HRID 1940481 reaction equation
[Cl:1][C:2]1[C:8]([O:9][CH2:10][C:11]#[CH:12])=[CH:7][C:5]([NH2:6])=[C:4]([F:13])[CH:3]=1.[CH:14]12[CH2:19][CH:18]1[CH2:17][NH:16][CH:15]2[C:20](O)=[O:21].C[Al](C)C.O>C(Cl)Cl>[Cl:1][C:2]1[C:8]([O:9][CH2:10][C:11]#[CH:12])=[CH:7][C:5]([NH:6][C:20]([CH:15]2[NH:16][CH2:17][CH:18]3[CH:14]2[CH2:19]3)=[O:21])=[C:4]([F:13])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 37794533-Azabicyclo[3.1.0]hexane-2-carboxylic acidHCID 13272927Benzenamine, 4-chloro-2-fluoro-5-(2-propynyloxy)-HCID 16682925Trimethylaluminum

Product 1

HCID 21462365N-[4-chloro-2-fluoro-5-(2-propynyloxy)phenyl]-3-azabicyclo-[3.1.0]hexane-2-carboxamideYield 35.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

To a mixture of 2.36 g (11.79 mmol) of 4-chloro-2-fluoro-5-(2-propynyl)oxyaniline and 1.5 g (11.79 mmol) of (±)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid in methylene chloride (150 mL) stirred under nitrogen and cooled to 5° C. was added trimethylaluminum dropwise (2.0M, 11.8 mL, 23.58 mmol). The resultant mixture was stirred at room temperature for 48 h. Water (100 mL) was added dropwise at ice-bath temperature. The solid inorganic material which formed was filtered, and the filtrate was dried (MgSO4) and evaporated under reduced pressure to dryness. Flash chromatography on silica gel yielded 1.3 g of the product of Step F as a tan solid; m.p. 113°-115° C. IR (mineral oil, cm-1): 1687.1 (C=O); 2123.5 (C≡C).

Workup

  1. customThe solid inorganic material which formed
  2. filtrationwas filtered
  3. dry with materialthe filtrate was dried (MgSO4)
  4. customevaporated under reduced pressure to dryness

Sources & evidence

ORD record
ord-ae08175ea3e641f09d82f329f5904dba
Source dataset
uspto-grants-1997_12
Patent number
US05700761

Reaction notes

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