Carbon Dioxide → 4-Cyclopropylmethoxy-N-((S)-6-formyl-1,2,3,4-tetrahydronaphthalen-2-yl)benzamide

HRID 77413Notes

Reaction equation

HRID 77413 reaction equation
BrC1C=C2C(=CC=1)C[C@@H](NC(=O)C1C=CC(OCC3CC3)=CC=1)CC2.C(=O)=O.C[Li].C([Li])CCC.[CH2:36]([O:40][C:41]1[CH:61]=[CH:60][C:44]([C:45]([NH:47][C@H:48]2[CH2:57][CH2:56][C:55]3[C:50](=[CH:51][CH:52]=[C:53]([CH:58]=[O:59])[CH:54]=3)[CH2:49]2)=[O:46])=[CH:43][CH:42]=1)[CH2:37][CH2:38][CH3:39]>O.C(O)(=O)C.CN(C=O)C.C1COCC1>[CH:37]1([CH2:36][O:40][C:41]2[CH:42]=[CH:43][C:44]([C:45]([NH:47][C@H:48]3[CH2:57][CH2:56][C:55]4[C:50](=[CH:51][CH:52]=[C:53]([CH:58]=[O:59])[CH:54]=4)[CH2:49]3)=[O:46])=[CH:60][CH:61]=2)[CH2:39][CH2:38]1

Participants

10

Reactant 5

HCID 280Carbon DioxideHCID 66663484N-((S)-6-Bromo-1,2,3,4-tetrahydronaphthalen-2-yl)-4-cyclopropylmethoxybenzamideHCID 86762749HCID 86762749, compoundHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 867627484-Cyclopropylmethoxy-N-((S)-6-formyl-1,2,3,4-tetrahydronaphthalen-2-yl)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-cyclopropylmethoxy-benzamide (5.20 g) and THF (120 ml) was cooled to −78° C. (dry ice bath), and a solution of methyllithium (8.9 ml; 1.6 M in diethyl ether) was added dropwise. One minute after the addition had ended, a solution of butyllithium (5.7 ml; 2.5 M in toluene) was added dropwise. One minute after the addition had ended, DMF (2.85 g) and, after a further 30 seconds, acetic acid (1.5 ml) were added. 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 349.43 (C22H23NO3); MS (ESI): 350 (M+H+). 4-Butoxy-N—((S)-6-formyl-1,2,3,4-tetrahydronaphthalen-2-yl)benzamide can also be prepared analogously.

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 349.43 (C22H23NO3)

Sources & evidence

ORD record
ord-cc7811fedaf243c5956de8e4b083cd4b
Source dataset
uspto-grants-2014_09
Patent number
US08841290B2

Reaction notes

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