Diisobutylaluminum hydride → HCID 67461800, compound

HRID 1191146Notes

Reaction equation

HRID 1191146 reaction equation
[CH3:1][C:2]([CH3:6])([CH3:5])[CH2:3][NH2:4].CC(C[AlH]CC(C)C)C.[C:16]([O:20][C:21]([N:23]1[CH2:29][CH2:28][C:27]2[C:30]([NH:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([S:43][CH2:44][C:45](OC)=[O:46])=[CH:39][CH:38]=3)=[C:31]([Cl:34])[CH:32]=[CH:33][C:26]=2[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>C1COCC1.CCOC(C)=O>[C:16]([O:20][C:21]([N:23]1[CH2:29][CH2:28][C:27]2[C:30]([NH:35][CH2:36][C:37]3[CH:38]=[CH:39][C:40]([S:43][CH2:44][C:45](=[O:46])[NH:4][CH2:3][C:2]([CH3:6])([CH3:5])[CH3:1])=[CH:41][CH:42]=3)=[C:31]([Cl:34])[CH:32]=[CH:33][C:26]=2[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 79882NeopentylamineHCID 58495581HCID 58495581, compound

Product 1

HCID 67461800HCID 67461800, compoundYield 66.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 2,2-dimethyl-propylamine (0.1 mL, 0.84 mmol) in anhydrous THF (0.6 mL) under nitrogen. Cool the solution at 0° C. and add DIBAL-H (0.79 mL, 0.79 mmol, 1M solution in toluene). Allow the mixture warm up to room temperature and stir for 2 h. Add this complex to a solution of 3-(tert-butoxycarbonyl)-7-chloro-6-(4-methoxycarbonylmethylthio-benzylamino)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (70 mg, 0.14 mmol) in THF (0.3 mL) and stir at room temperature overnight. Dilute with EtOAc and quench with 5% aqueous KHSO4. Dry the organic phase over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (4:1) to obtain the desired intermediate as an oil (51 mg, 65%).

Workup

  1. temperatureAllow the mixture warm up to room temperature
  2. stirringstir at room temperature overnight
  3. customquench with 5% aqueous KHSO4
  4. dry with materialDry the organic phase over MgSO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (4:1)

Sources & evidence

ORD record
ord-17a24f2de3664aa18611393c6f7b83e1
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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