Hydrochloric Acid → HCID 70007019, compound

HRID 276085

Reaction equation

HRID 276085 reaction equation
[H-].[Na+].[C:3]([NH:13][C@H:14]([C:17]([OH:19])=[O:18])[CH2:15][OH:16])([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[C:20]1([C:26]2[O:27][CH:28]=[C:29]([CH2:31][CH2:32][O:33][C:34]3[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=3)[CH2:37]Br)[N:30]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl>CO.CN(C=O)C.C1COCC1>[C:20]1([C:26]2[O:27][CH:28]=[C:29]([CH2:31][CH2:32][O:33][C:34]3[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=3)[CH2:37][O:16][CH2:15][C@@H:14]([C:17]([OH:19])=[O:18])[NH:13][C:3]([O:5][CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[O:4])[N:30]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 100310N-(Benzyloxycarbonyl)-L-serineHCID 18617241HCID 18617241, compound

Product 1

HCID 70007019HCID 70007019, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

0.448 g of 60% NaH/oil (0.27 g, 11.1 mM of NaH) was added to 40 mL of dry THF and cooled to 0° C. 1.21 g (5.08 mM of CBZ-serine was added dropwise as a dry DMF solution (10 mL) over 5 minutes. The resulting mixture was stirred at 0° C. for 1 hr. 2.00 g (5.58 mmoles) of 3-[2-(2-phenyl-4-oxazolyl)ethoxy]benzyl bromide, prepared as described in Example 22, Part B, was also added dropwise as a dry DMF solution (10 mL) over 5 minutes. The final mixture was stirred for 5 h at 0° C. and was then allowed to warm to ambient over 12 h. The reaction was quenched with 20 mL of methanol and one equivalent of HCl. After concentrating to a small volume under reduced pressure, the mixture was diluted with 200 mL EtOAc, washed with 200 mL water (2×) and 200 mL brine. The organic phase was dried over MgSO4, filtered and concentrated to a yellow, opaque oil. The product was purified using silica column chromatography, (25:5:1 CHCl3:MeOH:NH4OH>>>3:4 MeOH:EtOAc), and recrystallized from Et2O. to provide 714 mg 49.6%) of product as a white, waxy solid.

Workup

  1. temperatureto warm
  2. waitto ambient over 12 h
  3. concentrationAfter concentrating to a small volume under reduced pressure
  4. additionthe mixture was diluted with 200 mL EtOAc
  5. washwashed with 200 mL water (2×) and 200 mL brine
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to a yellow, opaque oil
  9. customThe product was purified
  10. customrecrystallized from Et2O
  11. customto provide 714 mg 49.6%) of product as a white, waxy solid

Sources & evidence

ORD record
ord-febd646685e4425eba394bb7fd54bc60
Source dataset
uspto-grants-2002_03
Patent number
US06353027B1

Linked notes

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