Dimethylformamide → HCID 59003118, compound

HRID 2353881Notes

Reaction equation

HRID 2353881 reaction equation
C([Li])CCC.[CH:6]([O:9][C:10]([N:12]1[CH2:18][CH2:17][CH2:16][CH:15]([N:19]([C:35](=[O:37])[CH3:36])[CH2:20][C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[C:14]2[CH:38]=[CH:39][C:40](Br)=[CH:41][C:13]1=2)=[O:11])([CH3:8])[CH3:7].CN(C)[CH:45]=[O:46].[BH4-].[Na+]>O1CCCC1.C(OCC)(=O)C.CO>[C:35]([N:19]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1)[CH:15]1[CH2:16][CH2:17][CH2:18][N:12]([C:10]([O:9][CH:6]([CH3:8])[CH3:7])=[O:11])[C:13]2[CH:41]=[C:40]([CH2:45][OH:46])[CH:39]=[CH:38][C:14]1=2)(=[O:37])[CH3:36]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 4311764Sodium borohydrideHCID 59003154Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 59003118HCID 59003118, compoundYield 8.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Add butyl lithium (0.157 mL, 0.252 mmol, 1.6 M in hexanes) dropwise to a solution of isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-bromo-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.100 g, 0.168 mmol) in tetrahydrofuran (2 mL) under nitrogen at −78° C. and stir for 1 h. Add N,N-dimethylformamide (0.052 mL, 0.672 mmol) dropwise to the cold solution and stir for 40 min at −78° C. then warm to room temperature. Quench the reaction with saturated aqueous ammonium chloride (10 mL) and dilute with ethyl acetate (20 mL). Separate the layers and wash the organic layer with water (2×30 mL) and brine (30 mL), then dry over sodium sulfate, filter and remove solvent under reduced pressure to provide the crude aldehyde. Dissolve the crude aldehyde (0.091 g, 0.167 mmol) in methanol (3 mL) and add sodium borohydride (0.019 g, 0.501 mmol) in one portion at room temperature. After stirring for 3 h, dilute the reaction with ethyl acetate (25 mL) and wash with brine (40 mL), then dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the crude material by chromatography on silica gel, eluting with acetonitrile to provide the title compound as an off-white solid (0.008 g, 8%): ESI MS 547 (M+H).

Workup

  1. customQuench
  2. customthe reaction with saturated aqueous ammonium chloride (10 mL)
  3. customSeparate the layers
  4. washwash the organic layer with water (2×30 mL) and brine (30 mL)
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. customremove solvent under reduced pressure
  8. customto provide the crude aldehyde
  9. stirringAfter stirring for 3 h
  10. additiondilute
  11. washwash with brine (40 mL)
  12. dry with materialdry the organic layer over sodium sulfate
  13. filtrationfilter
  14. customremove the solvent under reduced pressure
  15. customPurify the crude material by chromatography on silica gel
  16. washeluting with acetonitrile

Sources & evidence

ORD record
ord-133b88155e474c7690b1d8c824119116
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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