Citric Acid → HCID 15542878, compound

HRID 2269903Notes

Reaction equation

HRID 2269903 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)([CH2:13][CH:14]=O)[C:9]1=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[F:35][C:36]1[CH:59]=[CH:58][C:39]([CH2:40][N:41]2[C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=3[N:43]=[C:42]2[C:50](N2CCCCC2)=[O:51])=[CH:38][CH:37]=1.[C:60](O)(=O)[CH2:61][C:62]([CH2:67][C:68](O)=O)(C(O)=O)O.C([BH3-])#[N:74].[Na+].[NH4+].[Cl-]>CO>[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:74]2[CH2:68][CH2:67][CH:62]([C:50]([C:42]3[N:41]([CH2:40][C:39]4[CH:58]=[CH:59][C:36]([F:35])=[CH:37][CH:38]=4)[C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=4[N:43]=3)=[O:51])[CH2:61][CH2:60]2)([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:21][CH:22]=2)[C:9]1=[O:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 311Citric AcidHCID 25517Ammonium ChlorideHCID 5003444Sodium cyanoborohydrideHCID 18333230HCID 18333230, compoundHCID 70238369HCID 70238369, compound

Product 1

HCID 15542878HCID 15542878, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
2.5 °C

Procedure

Combine 1-benzyl-3-(4-trifluoromethyl-phenylmethyl)-3-(2-oxo-ethyl)-2-oxo-pyrrolidine (1.70 g, 4.15 mmol) and [1-(4-fluoro-benzyl)-1H-benzoimidazole-2-carbonyl]-piperidine trifluoroacetic acid salt (1.40 g, 3.11 mmol) in methanol (30 mL). Stir in freshly crushed 3 Å sieves. Cool the reaction mixture to 0-5° C. and add citric acid until pH=5. Add sodium cyanoborohydride (393 mg, 5.60 mmol) in portions. Stir overnight, allowing the reaction mixture to warm to room temperature. Pour solution into saturated NH4Cl, stir vigorously and extract with CH2Cl2. Separate the organic layer, extract with 1N NaOH, dry over Na2SO4, filter and concentrate in vacuo. Chromatograph the residue on silica gel eluting sequentially with 10% methanol/dichloromethane (with 0.1% concentrated NH4OH), then with 40% methanol. Further purify by chromatographing the residue on silica gel eluting sequentially with 20% ethyl acetate/hexane, then with methanol/ethyl acetate/hexane(20/20/60, with 0.1% concentrated NH4OH). Recrystallize from hexane to obtain the title compound as a white solid: mp; 104.5-106.0° C.; Rf=0.16 (silica gel, 10% MeOH/CH2Cl2 with 0.1% concentrated NH4OH). Elemental Analysis calculated for C41H40F6N4O2: C 65.98; H 4.72; N 2.85; Found: C 66.16; H 4.61; N 2.80.

Workup

  1. stirringStir overnight
  2. temperatureto warm to room temperature
  3. extractionextract with CH2Cl2
  4. customSeparate the organic layer
  5. extractionextract with 1N NaOH
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customFurther purify by chromatographing the residue on silica gel eluting sequentially with 20% ethyl acetate/hexane
  10. customRecrystallize from hexane

Sources & evidence

ORD record
ord-d52ab676f20047d58961691e9fb57486
Source dataset
uspto-grants-2001_12
Patent number
US06329392B1

Reaction notes

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