Citric Acid → HCID 66813544, compound

HRID 1098213Notes

Reaction equation

HRID 1098213 reaction equation
[H-].[Na+].[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([OH:30])[C:26]([O:28][CH3:29])=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[CH:42]=[C:43]([CH:46]=[CH:47][C:48]=3[CH3:49])[C:44]#[N:45])[N:39]=[CH:40][C:33]=12.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O.CCOC(C)=O>[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([O:30][C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[CH:42]=[C:43]([C:44]#[N:45])[CH:46]=[CH:47][C:48]=3[CH3:49])[N:39]=[CH:40][C:33]=12)[C:26]([O:28][CH3:29])=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 57504679HCID 57504679, compoundHCID 59279512(S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate

Product 1

HCID 66813544HCID 66813544, compoundYield 26.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (108 mg, 2.69 mmol) was added to (S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (795 mg, 1.97 mmol) (Intermediate AB3) in anhydrous THF (20 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 3-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-4-methylbenzonitrile (Intermediate AM2) (484 mg, 1.79 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was neutralised with 1M citric acid and the reaction mixture diluted with water (10 mL) and EtOAc (30 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (2×30 mL). The combined organics were washed with saturated brine (75 mL),dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 30 to 50% Et2O in isohexane to afford the product (300 mg, 26.3%). m/z (ES+) (M+H)+=636.5; HPLC tR=3.65 min.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 1 hour
  3. customThe organic layer was separated
  4. extractionthe aqueous layer re-extracted with EtOAc (2×30 mL)
  5. washThe combined organics were washed with saturated brine (75 mL),dried (MgSO4),
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash silica chromatography, elution gradient 30 to 50% Et2O in isohexane

Sources & evidence

ORD record
ord-41ecd95ff12b4ae180736a079f15ce38
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

Loading…