Diethylaluminum chloride → HCID 9846518, compound

HRID 1633586Notes

Reaction equation

HRID 1633586 reaction equation
[C:1]([NH:8][C@@H:9]([C:17](O)=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3]C(C)(C)C)=O.CC[Al](Cl)[CH2:23][CH3:24].[CH:26]1[CH:27]=[CH:28]C2N(O)N=N[C:30]=2[CH:31]=1.[CH3:36][O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.C[N+]1([O-])CCOCC1>CN(C=O)C.C(OCC)(=O)C>[CH2:10]([C@@H:9]([NH:8][C:1]([C:23]1([CH3:24])[CH2:28][CH2:27][CH2:26][CH2:31][CH2:30]1)=[O:3])[CH2:17][N:47]1[CH2:48][CH2:49][CH:44]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[O:37][CH3:36])[CH2:45][CH2:46]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

8

Reactant 5

HCID 7277Diethylaluminum chlorideHCID 757711-HydroxybenzotriazoleHCID 82029Methyl morpholine oxideHCID 5447384-(2-Methoxyphenyl)piperidineHCID 637610Boc-D-phenylalanine

Product 1

HCID 9846518HCID 9846518, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Boc-D-phenylalanine (2.0 g, 7.54 mmol), DEAC (1.45 g, 7.54 mmol), and HOBT (1.53 g, 11.3 mmol) in DMF (20 mL) at 0° C. was added 4-(2-methoxyphenyl)piperidine (1.88 g, 8.29 mmol) followed by the addition of NMO (1.4 mL, 12.8 mmol). The mixture was allowed to stir under nitrogen overnight at ambient temperature, diluted with ethyl acetate (50 mL) and washed with 0.1N HCl (20 mL), saturated NaHCO3 (20 mL), H2O (25 mL) and brine. The organic phase was dried over anhydrous Na2SO4, filtered and concentrated under vacuum to yield the required product (100%). This was stirred in 4.0M HCl/dioxane (40 mL) overnight and concentrated to afford the hydrochloride salt of the free amine. The amide was dissolved in THF (30 mL) and reduced by the addition of 1.0M LAH/THF (23 mL) at 0° C. After stirring overnight, the reaction was quenched by the addition of saturated NH4Cl, filtered through celite, dried over anhydrous Na2SO4, filtered and concentrated to yield the required product. 1-Methylcyclohexanecarboxylicacid chloride was added to a solution of the amine (1.22 g, 3.76 mmol) and triethylamine (1.1 mL, 7.5 mmol) in dichloromethane (20 mL) at 0° C. The reaction mixture was allowed to stir under nitrogen overnight at ambient temperature, concentrated under vacuum, diluted with ethyl acetate (50 mL) and washed with H2O (2×25 mL) then brine. The organic phase was dried over anhydrous Na2SO4, filtered and concentrated under vacuum to yield crude product. Purification by flash chromatography (elution with ethyl acetate/hexanes) yielded 1.1 g of the titled free base. The fumarate salt was prepared and crystallized yielding 0.81 g of the title compound as a pale yellow solid, m.p. 77-79° C.

Workup

  1. washwashed with 0.1N HCl (20 mL), saturated NaHCO3 (20 mL), H2O (25 mL) and brine
  2. dry with materialThe organic phase was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-6a2d1603fce344f190fbe7818b594d00
Source dataset
uspto-grants-2003_01
Patent number
US06503928B2

Reaction notes

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