Sodium hydride → HCID 86649378, compound

HRID 2191211Notes

Reaction equation

HRID 2191211 reaction equation
[CH3:1][C:2]1[CH:29]=[C:28]([CH3:30])[C:5]2[N:6]([C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[CH2:7][CH2:8][CH2:9][C@H:10]([NH:11][C:12]3[N:13]=[N:14][N:15]([CH3:17])[N:16]=3)[C:4]=2[CH:3]=1.[H-].[Na+].CC(C)([O-])C.[K+].[F:39][C:40]([F:54])([F:53])[C:41]1[CH:42]=[C:43]([CH:46]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:48]=1)[CH2:44]Br>CN(C=O)C.C1COCC1>[F:39][C:40]([F:53])([F:54])[C:41]1[CH:42]=[C:43]([CH:46]=[C:47]([C:49]([F:52])([F:50])[F:51])[CH:48]=1)[CH2:44][N:11]([C:12]1[N:13]=[N:14][N:15]([CH3:17])[N:16]=1)[C@H:10]1[CH2:9][CH2:8][CH2:7][N:6]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[C:5]2[C:28]([CH3:30])=[CH:29][C:2]([CH3:1])=[CH:3][C:4]1=2

Participants

7

Reactant 4

HCID 24758Sodium hydride3×HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 23665647Potassium tert-butoxideHCID 66599117HCID 66599117, compound

Product 1

HCID 86649378HCID 86649378, compoundYield 121.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Charge a vial with (S)-benzyl 7,9-dimethyl-5-(2-methyl-2H-tetrazol-5-ylamino)-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate (100 mg 246 μmoles), NaH (23 mg 60% in mineral oil, 575.1 μmoles) and THF (9.2 ml, 24.6 mmoles). (Alternatively, potassium tert-butoxide in DMF can be used in place of NaH and THF.) Stir the reaction mixture at RT for 10 m. Add 3,5 bis(trifluoromethyl)benzylbromide (173.8 mg 566.2 μmoles) dropwise over 30 min. After about 19 h, add NaH (10 mg, 60% mineral oil) and stir for an additional 1 h. Partition the reaction mixture between EtOAc (50 mL) and brine (2×25 mL). Collect the organic layers and dry over Na2SO4. Filter and then concentrate the filtrate to yield an oil. Partition the oil between ACN (50 mL) and heptane (2×25 mL). Collect the CAN layer; dry to yield an oil (189 mg) of the title compound.

Workup

  1. stirringstir for an additional 1 h
  2. customPartition the reaction mixture between EtOAc (50 mL) and brine (2×25 mL)
  3. customCollect the organic layers
  4. dry with materialdry over Na2SO4
  5. filtrationFilter
  6. concentrationconcentrate the filtrate
  7. customto yield an oil
  8. customPartition the oil between ACN (50 mL) and heptane (2×25 mL)
  9. customCollect the CAN layer
  10. customdry

Sources & evidence

ORD record
ord-2c7963344ed94ba9aa75e0769b93c6ec
Source dataset
uspto-grants-2012_12
Patent number
US08329688B2

Reaction notes

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