Ethyl Acetate → HCID 56595566, compound

HRID 2095359Notes

Reaction equation

HRID 2095359 reaction equation
[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:13][CH2:12][C@H:11]1[CH2:14][O:15][C:16]1[CH:17]=[N:18][CH:19]=[C:20]([C:22]#[C:23][Si](C)(C)C)[CH:21]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].CCOC(C)=O.CCCCCC.CCOC(C)=O>CO>[C:3]([O:7][C:8]([N:10]1[CH2:13][CH2:12][C@H:11]1[CH2:14][O:15][C:16]1[CH:17]=[N:18][CH:19]=[C:20]([C:22]#[CH:23])[CH:21]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 21226206Ethyl acetate hexaneHCID 56595565HCID 56595565, compound

Product 1

HCID 56595566HCID 56595566, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

In a 50 mL round-bottom flask with stir bar, a solution of KOH (174 mg) in methanol (4 mL) was added to a solution of 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[(trimethylsilyl)ethynyl]pyridine (560 mg, 1.55 mmol) in methanol (1 mL). The flask was loosely closed with a rubber stopper, and the mixture was stirred at room temperature for 3 h. A TLC taken after 105 min (silica gel, EtOAc/hexane 55:45) showed traces of starting material (Rf 0.6) and a new spot (Rf 0.5). The mixture was evaporated and the residue directly chromatographed on silica gel (24×2.5 cm, EtOAc/hexane 1:1). The product-containing fractions were evaporated, and the residue was dried (35° C./14 torr) to obtain 473 mg (nominally 106%) of the product, an orange-brown oil which darkened upon standing and appeared to be too unstable for more stringent drying. The excess mass balance was represented by EtOAc as shown by 1H NMR. The material was suitable in this form for the subsequent reaction. 1H NMR (CDCl3, TMS, 250 MHz) δ 8.36-8.29 (m, 2H), 7.33 (dd, 1H, J=1.6, 2.7 Hz), 4.51 (m, 1H), 4.34 (m, 1H), 4.13 (dd, 1H, J=2.9, 10.1 Hz), 3.89 (t, 2H, J=7.6 Hz), 3.20 (s, 1H), 2.43-2.20 (m, 2H), 1.43 (s, 9H); 13C NMR (CDCl3, 62.5 MHz) δ 156.0, 154.3 (br), 145.1, 138.4, 123.5, 119.3 (br), 80.4, 80.0, 79.7, 68.7, 59.9, 47.0 (br), 28.3, 18.9.

Workup

  1. customThe flask was loosely closed with a rubber stopper
  2. stirringthe mixture was stirred at room temperature for 3 h
  3. customThe mixture was evaporated
  4. customthe residue directly chromatographed on silica gel (24×2.5 cm, EtOAc/hexane 1:1)
  5. customThe product-containing fractions were evaporated
  6. customthe residue was dried (35° C./14 torr)
  7. customto obtain 473 mg (nominally 106%) of the product
  8. customThe material was suitable in this form for the subsequent reaction

Sources & evidence

ORD record
ord-9441e1eb410548e887ebbb9ac7d45e02
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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