Citric Acid → HCID 17965983, compound

HRID 2253347Notes

Reaction equation

HRID 2253347 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([OH:29])([C:23]2[N:27]([CH3:28])[CH:26]=[N:25][CH:24]=2)[C:10](O[C@@H]2C[C@H](C)CC[C@H]2C(C)C)=[O:11])=[CH:5][CH:4]=1)#[N:2].[Li+].[BH4-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[OH:29][C:9]([C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)([C:23]1[N:27]([CH3:28])[CH:26]=[N:25][CH:24]=1)[CH2:10][OH:11]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 4148881Lithium borohydrideHCID 90994751HCID 90994751, compound

Product 1

HCID 17965983HCID 17965983, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

A mixture of Example 93B (2.15 g, 78% potency, 4.24 mmol) in THF (6.5 mL) was treated with a solution of 2M LiBH4 in THF (3.3 mL, 6.1 mmol), heated to 55° C. for 3 hours, cooled to room temperature, treated with 20% citric acid (12 mL), warmed to 50° C. for 30 minutes, and extracted with MTBE (2×20 mL). The aqueous phase was adjusted to pH >10 with 50% NaOH and extracted with 5:1 THF/ethyl acetate (2×30 mL). The combined organic phases were concentrated, treated with citric acid (1.0 g), and concentrated to a volume of approximately 6 mL. The solution was adjusted to pH >10 with 50% NaOH, stirred for 2 hours, and filtered. The filter cake was washed with water (2 mL) and dried under vacuum with an air bleed to provide 670 mg (61% potency, 40% potency adjusted yield) of the desired product as one enantiomer in high excess. MS (ACPI) m/e 244 (M+H)+; 1H NMR (CD3OD) δ 7.70 (d, 2H) 7.55 (s, 1H) 7.54 (d, 2H) 7.18 (s, 1H) 4.00 (d, 1H) 3.89 (d, 1H) 3.30 (s, 3H).

Workup

  1. temperaturecooled to room temperature
  2. temperaturewarmed to 50° C. for 30 minutes
  3. extractionextracted with MTBE (2×20 mL)
  4. extractionextracted with 5:1 THF/ethyl acetate (2×30 mL)
  5. concentrationThe combined organic phases were concentrated
  6. additiontreated with citric acid (1.0 g)
  7. concentrationconcentrated to a volume of approximately 6 mL
  8. filtrationfiltered
  9. washThe filter cake was washed with water (2 mL)
  10. customdried under vacuum with an air bleed
  11. customto provide

Sources & evidence

ORD record
ord-54ba71244a9043ea9495ba69aaefde19
Source dataset
uspto-grants-2008_01
Patent number
US07323570B2

Reaction notes

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