Citric Acid → HCID 86709847, compound

HRID 1771851Notes

Reaction equation

HRID 1771851 reaction equation
CN1[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8].C([O:11][CH3:12])=O.C(O[CH2:16][CH3:17])=O.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[Si](C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.FC(F)(F)C(O)=O>Cl[Cu].[Cl-].[Cl-].[Zn+2].C(O)(=O)C.O1CCCC1>[CH2:6]1[O:8][CH2:3][N:4]2[CH2:7][CH:16]=[CH:17][C:5]12[CH:12]=[O:11]

Participants

12

Reactant 7

HCID 311Citric AcidHCID 6397ChlorotrimethylsilaneHCID 6422Trifluoroacetic acidHCID 66611,3-Dimethyl-2-imidazolidinoneHCID 7865Methyl formateHCID 8025Ethyl formateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 86709847HCID 86709847, compound

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 3007855ZincchlorideCatalystHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In Step 3-2, the compound of Formula XIV is mixed with: (i) a solvent which is preferably 1,3-dimethyl-2-imidazolidinone (DMI) or tetrahydrofuran, (ii) methyl formate or ethyl formate; and (iii) optionally a Lewis acid, for example, CuCl or ZnCl2. When a Lewis acid is employed, typically the Lewis acid is added in amounts of up to about 1 eq. relative to the amount of the compound of Formula XIV employed. In some embodiments a Lewis acid is employed in this step to increase yield and simplify workup of the reaction mixture. Following the addition of the constituents, the reaction mixture is cooled to a temperature of from about [−100]° C. to about [−55]° C., then, maintaining the temperature of the reaction mixture, to the reaction mixture is added lithium bis(trimethylsilyl)amide (LiHMDS) followed by chlorotrimethylsilane (TMSCl). After addition is complete, the reaction mixture is warmed to a temperature of from about 0° C. to about [+10]° C. and combined with an aliquot of a citric acid or acetic acid solution. The resultant intermediate is treated with trifluoroacetic acid to obtain the pyrrolo[1,2-c]oxazole-7a-carbaldehyde of Formula XV.

Workup

  1. temperatureto increase
  2. customyield
  3. additionthe addition of the constituents
  4. temperaturethe reaction mixture is cooled to a temperature of from about [−100]° C
  5. temperature, then, maintaining the temperature of the reaction mixture
  6. additionAfter addition

Sources & evidence

ORD record
ord-eedfcec37ed348c4bb6fa7ac5b88761d
Source dataset
uspto-grants-2016_02
Patent number
US09249144B2

Reaction notes

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