Carbon Dioxide → N-((S)-6-formyl-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide

HRID 1913812Notes

Reaction equation

HRID 1913812 reaction equation
BrC1C=C2C(=CC=1)C[C@@H](NC(=O)C1C=CC(OC[C@@H]3CCCO3)=CC=1)CC2.C(=O)=O.C[Li].C([Li])CCC.[CH:38]([C:40]1[CH:41]=[C:42]2[C:47](=[CH:48][CH:49]=1)[CH2:46][C@H:45]([NH:50][C:51](=[O:65])[C:52]1[CH:57]=[CH:56][C:55]([O:58][CH2:59][C@@H:60]3[CH2:64][CH2:63][CH2:62][O:61]3)=[CH:54][CH:53]=1)[CH2:44][CH2:43]2)=[O:39].BrC1C=C2C(=CC=1)C[C@H](NC(=O)C1C=CC(OC[C@@H]3CCCO3)=CC=1)CC2>O.C(O)(=O)C.CN(C=O)C.C1COCC1>[CH:38]([C:40]1[CH:41]=[C:42]2[C:47](=[CH:48][CH:49]=1)[CH2:46][C@@H:45]([NH:50][C:51](=[O:65])[C:52]1[CH:57]=[CH:56][C:55]([O:58][CH2:59][C@@H:60]3[CH2:64][CH2:63][CH2:62][O:61]3)=[CH:54][CH:53]=1)[CH2:44][CH2:43]2)=[O:39]

Participants

11

Reactant 6

HCID 280Carbon DioxideHCID 67544434N-((R)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamideHCID 67545579HCID 67545579, compoundHCID 86762191N-((R)-6-formyl-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamideHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 86762190N-((S)-6-formyl-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-((S)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide (10.0 g) and THF (130 ml) was cooled to −78° C. (dry ice bath) and a solution of methyl lithium (18.9 ml; 1.6 M in diethyl ether) was added dropwise. One minute after the addition had ended, a solution of butyllithium (13.9 ml; 2.5 M in toluene) was added dropwise. One minute after the addition had ended, DMF (5.1 g) was added, and, after a further 30 seconds, acetic acid (4.5 ml). After warming to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic phases were dried over magnesium sulfate and concentrated. The product was thus obtained with the molecular weight of 379.46 (C23H25NO4); MS (ESI): 380 (M+H+). In an analogous manner, N-((R)-6-formyl-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide was prepared from N-((R)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide.

Workup

  1. additionOne minute after the addition
  2. additionOne minute after the addition
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phases were dried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe product was thus obtained with the molecular weight of 379.46 (C23H25NO4)

Sources & evidence

ORD record
ord-54d188d6fc6541219542492bf213711e
Source dataset
uspto-grants-2013_12
Patent number
US08609731B2

Reaction notes

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