Triethylamine → HCID 57535369, compound

HRID 1455592Notes

Reaction equation

HRID 1455592 reaction equation
[C:1](=O)(O)[O-:2].[Na+].Cl.[CH3:7][O:8][C:9](=[O:19])[C@@H:10]([NH2:18])[CH2:11][C:12]([F:17])([F:16])[CH2:13][CH2:14][CH3:15].[CH2:20]1[CH2:26][O:25][CH2:24][CH2:23][NH:22][CH2:21]1.Cl.C(N(CC)CC)C>C(#N)C>[CH3:7][O:8][C:9](=[O:19])[C@@H:10]([NH:18][C:1]([N:22]1[CH2:21][CH2:20][CH2:26][O:25][CH2:24][CH2:23]1)=[O:2])[CH2:11][C:12]([F:17])([F:16])[CH2:13][CH2:14][CH3:15]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 230902141,4-Oxazepane hydrochlorideHCID 87588165HCID 87588165, compound

Product 1

HCID 57535369HCID 57535369, compoundYield 59.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of Sodium bicarbonate (5.25 g), p-nitro chloroformate (5.03 g, 25 mmol) in acetonitrile (130 mL) under nitrogen is added (S)-2-Amino-4,4-difluoro-heptanoic acid methyl ester hydrochloride (5.79 g, 0.025 mol) and stirred at room temperature for 5 hr. Homomorpholine hydrochloride (3.61 g, 26.25 mmol) and triethyl amine (12.5 mL) are added and the reaction stirred overnight at room temperature. Solvent evaporated off under reduced pressure, crude partitioned between water (150 mL) and ethyl acetate (200 mL). Organic layer separated, washed with K2CO3 solution (150 mL), HCl (150 mL) and brine (150 mL). Organic layer separated, dried (MgSO4) and evaporated under reduced pressure. Crude purified by column chromatography eluting with v/v 1:1 to 8:2 ethyl acetate heptane followed by ethyl acetate to give (S)-4,4-Difluoro-2-[(perhydro-1,4-oxazepine4-carbonyl)-amino]-heptanoic acid methyl ester (4.8 g) as an oil.

Workup

  1. stirringthe reaction stirred overnight at room temperature
  2. customSolvent evaporated off under reduced pressure, crude
  3. custompartitioned between water (150 mL) and ethyl acetate (200 mL)
  4. customOrganic layer separated
  5. washwashed with K2CO3 solution (150 mL), HCl (150 mL) and brine (150 mL)
  6. customOrganic layer separated
  7. dry with materialdried (MgSO4)
  8. customevaporated under reduced pressure
  9. customCrude purified by column chromatography
  10. washeluting with v/v 1:1 to 8:2 ethyl acetate heptane

Sources & evidence

ORD record
ord-283f9a6d428945308f3cfca554b48314
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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