Ammonium Chloride → HCID 178423967, compound

HRID 241023Notes

Reaction equation

HRID 241023 reaction equation
C[O-].[Na+].[C:4]([C@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])#[N:5].[Cl-].[NH4+:22].[CH3:23][C:24]1([CH3:35])[CH2:29][CH:28]([C:30](OC)=[O:31])[C:27](=O)[CH2:26][CH2:25]1>CO>[OH:31][C:30]1[C:28]2[CH2:29][C:24]([CH3:35])([CH3:23])[CH2:25][CH2:26][C:27]=2[N:22]=[C:4]([C@H:6]2[CH2:10][CH2:9][CH2:8][N:7]2[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[N:5]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 10942334Sodium Methoxide2×HCID 11447561(r)-1-Cbz-2-cyanopyrrolidineHCID 12441545Methyl 5,5-dimethyl-2-oxocyclohexane-1-carboxylate

Product 1

HCID 178423967HCID 178423967, compoundYield 90.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To sodium methoxide (30 wt % in methanol, 8 mg, 0.05 mmol) was added a solution of (R)-benzyl 2-cyanopyrrolidine-1-carboxylate (189 mg, 0.82 mmol) in methanol (1 mL) at room temperature and the reaction mixture was stirred for one hour. Ammonium chloride (44 mg, 0.82 mmol) was introduced and the stirring was continued for an additional two hours, followed by the addition of methyl 5,5-dimethyl-2-oxocyclohexanecarboxylate (100 mg, 0.54 mmol) and sodium methoxide (30 wt % in methanol, 293 mg, 1.63 mmol). The stirring was continued for two more hours. The reaction mixture was quenched with water (10 mL), neutralized with 1 N hydrochloric acid and extracted with ethyl acetate (3×10 mL). The combined extract was washed with water (20 mL) and brine, dried over sodium sulfate, filtered, concentrated and purified by gradient flash chromatography (25% to 95% ethyl acetate in hexane) to give phenylmethyl(2R)-2-(4-hydroxy-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-1-carboxylate (186 mg, 90%). MS (EI) for C22H27N3O3: 381 (MH+).

Workup

  1. waitthe stirring was continued for an additional two hours
  2. customThe reaction mixture was quenched with water (10 mL)
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. extractionThe combined extract
  5. washwas washed with water (20 mL) and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by gradient flash chromatography (25% to 95% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-2be6dac6cdf64f85abf7fc7a37a09899
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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