Hydrochloric Acid → HCID 54327213, compound

HRID 342558Notes

Reaction equation

HRID 342558 reaction equation
[CH2:1]([N:8]1[CH:13]=[C:12]([CH3:14])[C:11](=[O:15])[N:10]([CH2:16][C:17]2([C:20](O)=[O:21])[CH2:19][CH2:18]2)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OC)=O.[BH4-].[Na+].Cl>O.[Cl-].[Na+].O.C1COCC1>[CH2:1]([N:8]1[CH:13]=[C:12]([CH3:14])[C:11](=[O:15])[N:10]([CH2:16][C:17]2([CH2:20][OH:21])[CH2:18][CH2:19]2)[C:9]1=[O:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 54554001HCID 54554001, compound

Product 1

HCID 54327213HCID 54327213, compoundYield 90.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1-(1-benzyl-5-methyl-2,4-dioxo-(1H,3H)-pyrimidin-3-ylmethyl)-1-cyclopropanecarboxylic acid (11 g, 35 mmol), triethylamine (6.46 mL, 45.6 mmol) and THF (138 mL) was cooled to 0° C. under argon and a mixture of methyl chloroformate (3.23 mL, 42 mmol) and THF (20 mL) was added at a rate such that the temperature of the reaction mixture remained at 0° C. The mixture was cooled 30 minutes with stirring at 0° to 2° C. and then filtered (washing through with THF (3×50 mL)). The combined filtrate was cooled to 0° C. under argon and added to a mixture of sodium borohydride (3.29 g, 87 mmol) and water (23.3 mL) at <10° C. The mixture was stirred 2 hours, diluted with water (20 mL), treated with 10% hydrochloric acid, diluted with brine (40 mL) and extracted with ethyl acetate (4×100 mL). The combined extracts were washed with brine, dried (MgSO4) and concentrated to dryness. The residue was purified by flash chromatography on silica gel eluting with hexane/ethyl acetate (7:3) to give 1-(1-benzyl-5-methyl-2,4-dioxo-(1H,3H)-pyrimidin-3-ylmethyl)cycloprop-1-ylmethanol (9.52 g, 31.7 mmol), m.p. 81.5° C.

Workup

  1. additionwas added at a rate such that the temperature of the reaction mixture
  2. customremained at 0° C
  3. temperatureThe mixture was cooled 30 minutes
  4. filtrationfiltered
  5. wash(washing through with THF (3×50 mL))
  6. temperatureThe combined filtrate was cooled to 0° C. under argon
  7. stirringThe mixture was stirred 2 hours
  8. extractionextracted with ethyl acetate (4×100 mL)
  9. washThe combined extracts were washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated to dryness
  12. customThe residue was purified by flash chromatography on silica gel eluting with hexane/ethyl acetate (7:3)

Sources & evidence

ORD record
ord-0183594a2f1a467b9f626e1392d99a19
Source dataset
uspto-grants-1999_01
Patent number
US05859014

Reaction notes

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