Hydrochloric Acid → HCID 69020371, compound

HRID 1374865Notes

Reaction equation

HRID 1374865 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]([CH:20]([NH:24]C(OC(C)(C)C)=O)[CH:21]([CH3:23])[CH3:22])=[N:8][CH:7]=1)=[O:5])[CH3:2].Cl.O1CCOCC1.[C:39]([O:43][C:44](=[O:50])[NH:45][CH2:46][CH2:47][CH:48]=O)([CH3:42])([CH3:41])[CH3:40].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]([CH:20]([NH:24][CH2:48][CH2:47][CH2:46][NH:45][C:44]([O:43][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:50])[CH:21]([CH3:23])[CH3:22])=[N:8][CH:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10910051tert-Butyl N-(3-oxopropyl)carbamateHCID 58783534HCID 58783534, compound

Product 1

HCID 69020371HCID 69020371, compoundYield 64.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 1-Benzyl-2-(1-tert-butoxycarbonylamino-2-methyl-propyl)-6-oxo-1,6-dihydro-pyrimidine-5-carboxylic acid ethyl ester (14.22 g from previous step) was added a solution of 4M HCl in 1,4-dioxane (50 mL, 200 mmol) and the reaction was stirred at room temperature for 2.0 h. The reaction was concentrated in vacuo and the residue was dissolved in water and washed with ether. The aqueous layer was basified with 1 N NaOH and extracted into ether. The ether layer was washed with water, dried (Na2SO4), and concentrated to give a crystalline orange solid. This solid (7.08 g, 21.5 mmol) was dissolved in dry CH2Cl2 (100 mL) and to this was added (3-Oxo-propyl)-carbamic acid tert-butyl ester (3.076 g, 17.76 mmol) in dry CH2Cl2 (50 mL) followed by portionwise addition of sodium triacetoxyborohydride (5.65 g, 26.64 mmol). The reaction was stirred for 72 h at room temperature under N2 at which time the reaction was made basic with saturated sodium bicarbonate. The layers were separated, the aqueous layer was extracted with methylene chloride, and the combined organics were washed with brine, dried (Na2SO4), and evaporated to dryness. The residue was purified by flash chromatography on silica gel (1:1 hexanes:EtOAc) to give the title compound as a pale yellow foam (5.59 g 32%, 3 steps). MS(ES+) m/e 487 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue was dissolved in water
  3. washwashed with ether
  4. extractionextracted into ether
  5. washThe ether layer was washed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto give a crystalline orange solid
  9. stirringThe reaction was stirred for 72 h at room temperature under N2 at which time the reaction
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted with methylene chloride
  12. washthe combined organics were washed with brine
  13. dry with materialdried (Na2SO4)
  14. customevaporated to dryness
  15. customThe residue was purified by flash chromatography on silica gel (1:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-181789b252a94df2b5c09f0f850ac37a
Source dataset
uspto-grants-2007_01
Patent number
US07166595B2

Reaction notes

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