Triethylamine → {2-[(2-Cyano-ethylcarbamoyl)-methyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester

HRID 1167948Notes

Reaction equation

HRID 1167948 reaction equation
C(OC(=O)C(C#N)=C1[CH2:10][C@@H:9]([CH3:11])[C@H:8](C)C1)C.[CH3:16][CH:17]([CH2:19][C@H:20]([CH2:25][NH2:26])[CH2:21][C:22]([OH:24])=O)[CH3:18].C(N(CC)CC)C.ClC(OCC(C)C)=O.[C:42]([OH:49])(=[O:48])/C=C/C(O)=O.[NH2:50][CH2:51][CH2:52][C:53]#[N:54]>C1COCC1.[OH-].[Na+]>[C:9]([O:49][C:42](=[O:48])[NH:26][CH2:25][CH:20]([CH2:21][C:22](=[O:24])[NH:54][CH2:53][CH2:52][C:51]#[N:50])[CH2:19][CH:17]([CH3:16])[CH3:18])([CH3:8])([CH3:10])[CH3:11]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 5486971PregabalinHCID 6433176Propanenitrile, 3-amino-, (2E)-2-butenedioate (1:1)HCID 12970148(trans)Cyan-(3,4-dimethyl-cyclopentylidene)-acetic acid ethyl ester

Product 1

HCID 86604928{2-[(2-Cyano-ethylcarbamoyl)-methyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 14798Sodium HydroxideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of compound 2 (8.0 g, 0.03 mol) (prepared in the usual manner from (BOC)2 and pregabalin) was taken up in 250 mL dry THF and cooled in an ice water bath. Triethyl amine (4.62 mL, 0.033 mol) was added followed by the addition of isobutyl chloroformate (4 mL, 0.031 mol). The reaction was stirred a 0° C. for about 15 minutes during which time a precipitate formed. In a separate flask was placed 3-aminoproprionitrile fumarate (3.95 g, 0.03 mol) in 35 mL of 1 M NaOH and 300 mL of THF. This mixture was cooled to 0° C. and treated with the mixed anhydride formed above in four portions. Before each portion was added, 35 mL of 1 M NaOH was added to the mixture. The reaction was stirred for 24 hours and was then concentrated to remove THF. The resulting aqueous was extracted with three times ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate. The solvents were removed under pressure to give 6.6 g green oil. MS(APCI) m/z 312 (M+1).

Workup

  1. temperaturecooled in an ice water bath
  2. customformed
  3. customIn a separate flask was placed
  4. temperatureThis mixture was cooled to 0° C.
  5. customformed above in four portions
  6. additionBefore each portion was added
  7. stirringThe reaction was stirred for 24 hours
  8. concentrationwas then concentrated
  9. customto remove THF
  10. extractionThe resulting aqueous was extracted with three times ethyl acetate
  11. washThe combined organic extracts were washed with brine
  12. dry with materialdried over magnesium sulfate
  13. customThe solvents were removed under pressure

Sources & evidence

ORD record
ord-fc3f35f6274c46808f59653729b99165
Source dataset
uspto-grants-2003_09
Patent number
US06620829B2

Reaction notes

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