Acetic Acid → HCID 86699924, compound

HRID 530486Notes

Reaction equation

HRID 530486 reaction equation
[CH3:1][C:2]1([O:8][C:9](=[O:12])[NH:10]N)[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.CC(O)=O.N([O-])=O.[Na+].N[C@@H:22]([C:26]([OH:28])=[O:27])[C@H:23]([CH3:25])[OH:24].C([O-])([O-])=O.[Na+].[Na+].Cl>O.CCOC(C)=O.O1CCOCC1>[OH:24][C@@H:23]([CH3:25])[C@@H:22]([NH:10][C:9]([O:8][C:2]1([CH3:1])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1)=[O:12])[C:26]([OH:28])=[O:27]

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 69435D-Threonine2×HCID 23668193Sodium NitriteHCID 86699923HCID 86699923, compound

Product 1

HCID 86699924HCID 86699924, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent4×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

In a round bottomed flask equipped with a magnetic stirrer (4-methyltetrahydropyran-4-yl)-N-aminocarbamate (0.540 g, 3.10 mmol), H2O (10 mL) and CH3COOH (0.35 mL, 6.20 mmol) were sequentially added. The resulting mixture was cooled to 0° C. and NaNO2 (0.354 g, 3.72 mmol) dissolved in H2O (2 mL) was added dropwise. The cloudy mixture was stirred for 1.5 h at rt. Dioxane (20 mL) followed by the D-threonine salt solution [prepared from D-threonine (0.554 g, 4.65 mmol) solution in H2O (4 mL) and Na2CO3 (1.34 g, 12.40 mmol)] were added to the mixture. After being left overnight at 45° C., the crude mixture was then cooled to rt, then H2O (30 mL) and AcOEt (80 mL) were added and, while maintaining a vigorous stirring, the pH was adjusted to 2 with 2M HCl solution. The phases were separated and the aqueous one washed with AcOEt (2×50 mL). The combined organic liquors were dried over Na2SO4 and concentrated to leave a light yellow oil (0.647 g, 80%), which was used in the next step without purification. MS (ESI) m/z: 284.1 [M−Na]+. 1H NMR (DMSO-d6): δ 1.09 (d, J=6.3 Hz, 3H), 1.47 (s, 3H), 1.63 (m, 2H), 1.99 (m, 2H), 3.61 (m, 5H), 3.90 (dd, J=9.4, 6.3 Hz, 1H), 4.09 (m, 1H), 6.53 (d, J=9.4 Hz, 1H), 12.20 (bs, 1H).

Workup

  1. additionwere sequentially added
  2. additionwas added dropwise
  3. additionwere added to the mixture
  4. waitAfter being left overnight at 45° C.
  5. temperaturewhile maintaining a vigorous stirring
  6. customThe phases were separated
  7. washthe aqueous one washed with AcOEt (2×50 mL)
  8. dry with materialThe combined organic liquors were dried over Na2SO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-1f358fc3bdd6497783497a3bf0a9ad3e
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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