Hydrochloric Acid → HCID 69059432, compound

HRID 1295060Notes

Reaction equation

HRID 1295060 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][CH2:3][C:2]2=O.[C:8](OCC)(=O)[C:9]([O:11][CH2:12][CH3:13])=[O:10].CC([O-])(C)C.[K+].Cl.[NH2:25][NH2:26].Cl.C(O)(C(F)(F)F)=O>CCO.C1COCC1.O.CC#N>[CH2:12]([O:11][C:9]([C:8]1[C:3]2[CH2:4][CH:5]3[CH2:6][CH:1]3[C:2]=2[NH:25][N:26]=1)=[O:10])[CH3:13]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acid2×HCID 7268Diethyl OxalateHCID 115031Hydrazinium chlorideHCID 549294Bicyclo[3.1.0]hexan-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 69059432HCID 69059432, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of bicyclo[3.1.0]hexan-2-one (9.24 g, 96.1 mmol) and diethyl oxalate (14.7 g, 101 mmol) in EtOH (250 mL) at rt under N2 was added a solution of KOt-Bu in THF (106 mL of a 1M solution, 106 mmol). The reaction was stirred for 3.5 h at which time hydrazine hydrochloride (7.90 g, 115 mmol) in H2O (40 mL) was added. The reaction mixture was stirred for 20 h at rt and acidified to pH ˜3 by the addition of HCl (6N aq.). The volatiles were removed in vacuo and the resulting solid was diluted with EtOAc (500 mL) and H2O (500 mL). The layers were separated and the aqueous phase was back-extracted with EtOAc (300 mL). The combined organics were washed with brine (400 mL), dried over MgSO4, filtered, and concentrated to a crude oil that was determined to be approximately 75–80% pure (wt./wt.) ester by 1H NMR. The title compound was used directly in the next reaction (aminolysis) without further purification. 1H NMR (400 MHz, CDCl3): δ 10.55 (1H, bs), 4.32 (2H, q, J=6.8 Hz), 2.96 (1H, dd, J=16.8, 6.0 Hz), 2.80 (1H, d, J=17.2 Hz), 2.23–2.13 (2H, m), 1.35 (3H, t, J=7.2 Hz), 1.15 (1H, m), 0.34 (1H, m). 13C APT NMR (partial) (100 MHz, CDCl3): δ up: 127.4, 61.2, 26.8, 16.8; down: 23.0, 15.4, 14.5. HPLC/MS: Discovery® C18 column (5μ, 50×2.1 mm), 5% v/v CH3CN (containing 1% v/v TFA) in H2O (containing 1% v/v TFA) gradient to 99% v/v CH3CN in H2O, 0.75 mL/min, tr=1.62 min, ESI+=193.1 (M+H).

Workup

  1. additionwas added
  2. customThe volatiles were removed in vacuo
  3. additionthe resulting solid was diluted with EtOAc (500 mL) and H2O (500 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was back-extracted with EtOAc (300 mL)
  6. washThe combined organics were washed with brine (400 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to a crude oil that
  10. customThe title compound was used directly in the next reaction (aminolysis) without further purification

Sources & evidence

ORD record
ord-6ee67e325c8d4db7a77a66b6df49bb6e
Source dataset
uspto-grants-2007_07
Patent number
US07241792B2

Reaction notes

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