Acetic Acid → HCID 59799078, compound

HRID 1013114Notes

Reaction equation

HRID 1013114 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:19]1[CH2:22][CH:21]([O:23][Si](C(C)(C)C)(C)C)[CH2:20]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)(=O)C>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:14])([F:13])[F:15])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:19]1[CH2:22][CH:21]([OH:23])[CH2:20]1

Participants

6

Reactant 3

HCID 176Acetic Acid3×HCID 2724141Tetrabutylammonium Fluoride3×HCID 86622857HCID 86622857, compound

Product 1

HCID 59799078HCID 59799078, compoundYield 72.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen mix 7-chloro-6-[3-(tert-butyldimethyl-silanyloxy)-azetidin-1-yl]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (594 mg, 1.29 mmol), 1 N tetrabutylammonium fluoride solution in THF (2.04 mL, 2.04 mmol), glacial acetic acid (0.2 mL, 3.33 mmol), 4 Å molecular sieve (650 mg) in anhydrous THF (18 mL). Stir at RT for 3 days. After the first day add more 1 N tetrabutylammonium fluoride solution in THF (2.04 mL, 2.04 mmol) and glacial acetic acid (0.2 mL, 3.33 mmol). After the second day add more 1 N tetrabutylammonium fluoride solution in THF (2.04 mL, 2.04 mmol) and glacial acetic acid (0.2 mL, 3.33 mmol). Stop the reaction on the third day. Dilute with EtOAc and wash with saturated aqueous sodium bicarbonate solution and 0.1 N NaOH. Extract the aqueous layer three times with EtOAc. Combine the EtOAc fractions, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 to 30:70 EtOAc:hexanes) to give the title compound (325 mg, 72%).

Workup

  1. customthe reaction on the third day
  2. washwash with saturated aqueous sodium bicarbonate solution and 0.1 N NaOH
  3. extractionExtract the aqueous layer three times with EtOAc
  4. dry with materialdry (sodium sulfate)
  5. concentrationconcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 10:90 to 30:70 EtOAc:hexanes)

Sources & evidence

ORD record
ord-39df05c2c0f5450ea61e6a796fc63117
Source dataset
uspto-grants-2011_07
Patent number
US07981882B2

Reaction notes

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