Hydrochloric Acid → HCID 21932004, compound

HRID 1469876Notes

Reaction equation

HRID 1469876 reaction equation
[Li]CCCC.N(C(C)C)C(C)C.[CH:13]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14]1.Br[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][Cl:29].Cl>C1COCC1.[Cl-].[Na+].O.O>[Cl:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C:13]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 960701-Bromo-5-chloropentaneHCID 13676038tert-Butyl cyclopropanecarboxylateHCID 178418339Butyllithium

Product 1

HCID 21932004HCID 21932004, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-70 °C

Procedure

Under an Ar atmosphere at 0° C., BuLi (2.5M in hexanes, 80 mL, 0.20 mol) was added dropwise to a solution of iPr2NH (27.2 mL, 194 mmol, distilled from NaOH) in dry THF (200 mL) in 30 min. The reaction mixture was stirred for 30 min, cooled to −70° C. and then, tert-butyl cyclopropanecarboxylate (prepared according to Kohlrausch, K. W. F.; Skrabal, R., Z. Elektrochem. Angew. Phys. Chem., 1937, 43, 282-285, 25.0 g, 176 mmol) was added dropwise in 30 min. The resultant mixture was allowed to warm up to −35° C., cooled again to −70° C. and then 1-bromo-5-chloropentane (36 mL, 50.7 g, 273 mmol) was added dropwise in 15 min. The reaction mixture was allowed to reach −5° C., stirred for 3 h, poured into a mixture of ice (100 mL), H2O (100 mL), brine (200 mL) and aqueous HCl (2M, 200 mL) and extracted with Et2O (2×300 mL). The combined organic layers were washed with a mixture of brine and saturated aqueous NaHCO3 (10:1, 300 mL), dried (Na2SO4) and evaporated in vacuo. The remaining oil was purified by fractional distillation under reduced pressure to give tert-butyl 1-(5-chloropentyl)-1-cyclopropanecarboxylate (31.5 g 73%) as a colorless liquid. bp: T=67-74° C. (p=0.001 mbar). 1H NMR (CDCl3): δ=3.52 (t, J=6.6 Hz, 2H), 1.77 (quintet, J=6.8 Hz, 2H), 1.48-1.38 (m, 6H), 1.42 (s, 9H), 1.10 (dd, J=6.5 Hz, 3.8 Hz, 2H), 0.59 (dd, J=6.6, 3.9 Hz, 2H). 13C NMR (CDCl3): δ=174.1, 79.9, 45.2, 34.2, 32.7, 28.2 (3×), 27.20, 27.17, 24.3, 15.4 (2×). FIRMS calcd for C13H24ClO2 (MH+): 247.1465, found: 247.1465.

Workup

  1. temperatureto warm up to −35° C.
  2. temperaturecooled again to −70° C.
  3. customto reach −5° C.
  4. stirringstirred for 3 h
  5. extractionextracted with Et2O (2×300 mL)
  6. washThe combined organic layers were washed with a mixture of brine and saturated aqueous NaHCO3 (10:1, 300 mL)
  7. dry with materialdried (Na2SO4)
  8. customevaporated in vacuo
  9. distillationThe remaining oil was purified by fractional distillation under reduced pressure

Sources & evidence

ORD record
ord-93d53c3ece014c878856fc15a2df99f9
Source dataset
uspto-grants-2015_04
Patent number
US09006290B2

Reaction notes

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