Water → HCID 11264804, compound

HRID 2105552Notes

Reaction equation

HRID 2105552 reaction equation
[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:14](=[O:15])[CH2:13][CH2:12][CH2:11][C:10]3[CH:16]=[CH:17][CH:18]=[CH:19][C:9]2=3)=[CH:5][CH:4]=1.[Li+].CC([N-:26][CH:27](C)C)C.[CH:30]([O:32][CH2:33]C)=[O:31].[OH2:35]>C1COCC1>[OH:35][N:26]([CH2:27][CH:13]1[C:14](=[O:15])[NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[CH2:11][CH2:12]1)[CH:33]=[O:32].[OH:31][CH2:30][CH:13]1[C:14](=[O:15])[N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:21][CH:20]=2)[C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[CH2:11][CH2:12]1

Participants

7

Reactant 4

HCID 962WaterHCID 8025Ethyl formateHCID 14749841,3,4,5-Tetrahydro-1-[(4-methoxyphenyl)methyl]-2H-1-benzazepin-2-oneHCID 2724682Lithium diisopropylamide

Product 2

HCID 11264804HCID 11264804, compoundHCID 69006818HCID 69006818, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

1-(4-Methoxy-benzyl)-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (0.71 mmol) synthesized as described in example 12 is dissolved in 5 mL of anhydrous THF and cooled down to −78° C. A solution of freshly prepared LDA (0.85 mmol) is added to the mixture slowly. After stirring at the same temperature for 10 minutes, the mixture is allowed to warm up to 0° C. for 30 minutes and then cooled down to −78° C. again. Ethyl formate (3.55 mmol) is added dropwise to the reaction mixture. After the addition, the mixture is stirred at −78° C. for 10 minutes and then the temperature is risen to 0° C. for 1 hour. The reaction is quenched by addition of 1 mL of a mixture of water and EtOH (1:1), concentrated and dried under reduced pressure for 24 hours. The residue is redissolved in 4 mL of anhydrous THF, Na(AcO)3BH (2.1 mmol) is added to the mixture and the resulting mixture is stirred at room temperature for 16 hours. The reaction mixture is poured into 20 mL of water and extracted with EtOAc (3×10 mL). The organic layers are combined, washed with brine and dried over MgSO4. Solvent is removed under vacuum and the residue is purified by flash column chromatography (silica gel) to provide the desired product 3-hydroxymethyl-1-(4-methoxy-benzyl)-1,3,4,5-tetrahydro-benzo[b]azepin-2-one as white solid. Yield: 45%. MS: (ES+): 312 [M+1].

Workup

  1. temperatureto warm up to 0° C. for 30 minutes
  2. temperaturecooled down to −78° C. again
  3. additionAfter the addition
  4. stirringthe mixture is stirred at −78° C. for 10 minutes
  5. waitthe temperature is risen to 0° C. for 1 hour
  6. customThe reaction is quenched by addition of 1 mL of a mixture of water and EtOH (1:1)
  7. concentrationconcentrated
  8. customdried under reduced pressure for 24 hours
  9. dissolutionThe residue is redissolved in 4 mL of anhydrous THF
  10. stirringthe resulting mixture is stirred at room temperature for 16 hours
  11. extractionextracted with EtOAc (3×10 mL)
  12. washwashed with brine
  13. dry with materialdried over MgSO4
  14. customSolvent is removed under vacuum
  15. customthe residue is purified by flash column chromatography (silica gel)

Sources & evidence

ORD record
ord-910797c5c1194d1ca22ebb930751a3cb
Source dataset
uspto-grants-2009_08
Patent number
US07579363B2

Reaction notes

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