Sodium Hydroxide → HCID 68291765, compound

HRID 1507971Notes

Reaction equation

HRID 1507971 reaction equation
[OH-].[Na+].[C:3]([O:7][C:8]([NH:10][C@@H:11]([C@H:13]([C:16]1[O:17][CH:18]=[C:19]([C:21]([O:23]C)=[O:22])[N:20]=1)[CH2:14][CH3:15])[CH3:12])=[O:9])([CH3:6])([CH3:5])[CH3:4]>C1COCC1>[C:3]([O:7][C:8]([NH:10][C@@H:11]([C@H:13]([C:16]1[O:17][CH:18]=[C:19]([C:21]([OH:23])=[O:22])[N:20]=1)[CH2:14][CH3:15])[CH3:12])=[O:9])([CH3:5])([CH3:6])[CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68291663HCID 68291663, compound

Product 1

HCID 68291765HCID 68291765, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1N aqueous sodium hydroxide (5.69 ml, 5.69 mmol) was added in one portion to a solution of methyl 2-((2R,3R)-2-((tert-butoxycarbonyl)amino)pentan-3-yl)oxazole-4-carboxylate (100 mg, 0.32 mmol) in anhydrous THF (1.11 ml). The reaction mixture was allowed to stir at room temperature for 3.5 hours before evaporating the organic in vacuo. The remaining aqueous portion was cooled to 0° C. and acidified to pH 4 using 1N HCl. The aqueous phase was then extracted with ethyl acetate (3×3 mL). The aqueous pH was re-checked and judged to be ˜pH 6-7. A small amount of 1N HCl was added to re-acidify the aqueous layer which was once again extracted with an additional portion of ethyl acetate (1×3 mL). The combined organics were dried (MgSO4) and evaporated in vacuo to give crude 2-((2R,3R)-2-((tert-butoxycarbonyl)amino)pentan-3-yl)oxazole-4-carboxylic acid (95 mg, 0.32 mmol, 100% yield) as a white solid which was used immediately in the next reaction. EDC (86 mg, 0.45 mmol) was added in one portion to a mixture of 2-((2R,3R)-2-((tert-butoxycarbonyl)amino)pentan-3-yl)oxazole-4-carboxylic acid (95 mg, 0.32 mmol) and HOBT (69 mg, 0.45 mmol) in anhydrous dichloromethane (5.0 ml) and the reaction allowed to stir at room temperature under a nitrogen atmosphere for 30 minutes. Ammonia was then bubbled through for approximately 5 minutes and the resulting white suspension allowed to stir at room temperature overnight. The reaction was then evaporated in vacuo and the residue partitioned between ethyl acetate (10 mL) and water (10 mL). The organic layer was then dried (MgSO4) and evaporated in vacuo to give tert-butyl((2R,3R)-3-(4-carbamoyloxazol-2-yl)pentan-2-yl)carbamate (95 mg, 0.32 mmol, 100% yield) which was used immediately in the next step. LC/MS: M+H+436.11, ret. time=1.89 min. Column: Phenomenex, 2.0×30 mm, 2.5-μm particles; Mobile Phase A: 10:90 methanol:water with 0.05% TFA; Mobile Phase B: 90:10 methanol:water with 0.05% TFA; Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a 0.75-minute hold at 100% B; Flow: 1.11 mL/min. HPLC: ret. time=2.73 min. Column: YMC CombiScreen ODS-A, 4.6×50 mm; Mobile Phase A: 10:90 methanol:water with 0.2% H3PO4; Mobile Phase B: 90:10 methanol:water with 0.2% H3PO4; Temperature: 50° C.; Gradient: 0-100% B over 4 minutes, then a 0.75-minute hold at 100% B; Flow: 4 mL/min.

Workup

  1. custombefore evaporating the organic in vacuo
  2. temperatureThe remaining aqueous portion was cooled to 0° C.
  3. extractionThe aqueous phase was then extracted with ethyl acetate (3×3 mL)
  4. additionA small amount of 1N HCl was added
  5. extractionwas once again extracted with an additional portion of ethyl acetate (1×3 mL)
  6. dry with materialThe combined organics were dried (MgSO4)
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-e761a9e772eb413c8d6b75ee6463420c
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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