Hydrochloric Acid → HCID 86684903, compound

HRID 2402893Notes

Reaction equation

HRID 2402893 reaction equation
[CH3:1][C:2]1([C:5]([N:7]2[CH2:12][C@@H:11]3[CH2:13][C@H:8]2[C:9](=[O:14])[O:10]3)=[O:6])[CH2:4][CH2:3]1.Cl.[NH2:16][C:17]1([C:20]#[N:21])[CH2:19][CH2:18]1.C(C(CCCC)C([O-])=O)C.[Na+].Cl.[Cl-].[Na+]>O.ClCCl>[C:20]([C:17]1([NH:16][C:9]([C@@H:8]2[CH2:13][C@H:11]([OH:10])[CH2:12][N:7]2[C:5]([C:2]2([CH3:1])[CH2:4][CH2:3]2)=[O:6])=[O:14])[CH2:19][CH2:18]1)#[N:21]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 23672331Sodium 2-ethylhexanoateHCID 86684900HCID 86684900, compound

Product 1

HCID 86684903HCID 86684903, compoundYield 91.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

(1S,4S)-5-(1-Methyl-cyclopropanecarbonyl)-2-oxa-5-aza-bicyclo[2.2.1]heptan-3-one (100 g, 512 mmol), 1-amino-cyclopropanecarbonitrile hydrochloride (62.0 g, 523 mmol), and sodium 2-ethylhexanoate (97%, 96.5 g, 563 mmol) were dissolved in water (500 mL). The mixture was stirred for 16 h at 50° C. After cooling to room temperature, dichloromethane (500 mL) was added, the mixture was acidified by addition of hydrochloric acid (25% m/m, 13.8 mL, 106 mmol), and sodium chloride (120 g) was added. The mixture was stirred for 1 h, phases were separated, the aqueous layer was extracted with dichloromethane (3×330 mL) and the combined organic extracts were concentrated in vacuo to a volume of ca. 1.1 L. Ethyl acetate (1.1 L) was added, the mixture was concentrated in vacuo to a volume of ca. 1 L and heptane (1 L) was added within 30 min. The resulting suspension was stirred for 2 h at 2° C., filtered, the precipitate was washed with cold ethyl acetate/heptane 1:1 (v/v, 340 mL) and heptane (340 mL) and dried in vacuo to afford the title compound as light yellow crystals (129.4 g, 90%). MS (ESI & APCI): m/z=278.1 [M+H]+. 1H NMR (CDCl3, 600 MHz): δ 0.60-0.65 (m, 2H), 0.89-0.92 (m, 1H), 0.95-0.98 (m, 1H), 1.20-1.26 (m, 2H), 1.33 (s, 3H), 1.50-1.57 (m, 2H), 2.13 (ddd, J=5.0 Hz, 9.0 Hz, 14.1 Hz, 1H), 2.39 (br d, J=14.3 Hz, 1H), 3.76 (dd, J=4.3 Hz, 11.6 Hz, 1H), 3.85 (d, J=11.6 Hz, 1H), 4.48-4.53 (m, 1H), 4.57 (d, J=9.0 Hz, 1H), 4.70 (br s, 1H), 7.92 (br s, 1H).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringThe mixture was stirred for 1 h
  3. customphases were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (3×330 mL)
  5. concentrationthe combined organic extracts were concentrated in vacuo to a volume of ca. 1.1 L
  6. additionEthyl acetate (1.1 L) was added
  7. concentrationthe mixture was concentrated in vacuo to a volume of ca. 1 L and heptane (1 L)
  8. additionwas added within 30 min
  9. stirringThe resulting suspension was stirred for 2 h at 2° C.
  10. filtrationfiltered
  11. washthe precipitate was washed with cold ethyl acetate/heptane 1:1 (v/v, 340 mL) and heptane (340 mL)
  12. customdried in vacuo

Sources & evidence

ORD record
ord-2b2835a7949f4e6e839aae60083fb1c6
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

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