Methyl chloroformate → HCID 71087059, compound

HRID 1523006Notes

Reaction equation

HRID 1523006 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]#[CH:17].[Li]CCCC.Cl[C:24]([O:26][CH3:27])=[O:25]>C1COCC1>[CH3:27][O:26][C:24](=[O:25])[C:17]#[C:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][O:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][O:1]1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 109116082H-Pyran, 2-(9-decynyloxy)tetrahydro-HCID 178418339Butyllithium

Product 1

HCID 71087059HCID 71087059, compoundYield 90.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A flame-dried round-bottomed flask was charged with 9-decyn-1-ol tetrahydropyranyl ether (1 equiv, 31.7 mmol, 7.55 g) and THF (40 mL), and cooled to −78° C. n-BuLi (1.1 equiv, 34.9 mmol, 21.8 mL of a nominally 1.6 M solution in hexanes) were added dropwise over 5 min. The reaction was stirred for 30 min at −78° C. and then added to a solution of methyl chloroformate (1.5 eq, 47.6 mmol, 4.50 g, 3.7 mL) in THF (20 mL) dropwise via cannula. The reaction was stirred for 30 min at −78° C., then warmed to rt over 1 h and quenched dropwise with H2O (40 mL). The layers were separated and the aqueous layer was extracted with Et2O (2×25 mL). The combined organic layers were dried with Na2SO4, evaporated in vacuo, and purified by flash column chromatography (step gradient, 5% EtOAc/Hex to 10% EtOAc/Hex) to afford Methyl-11-[(tetrahydro-2H-pyran-2-yl)oxy]-undecynoate (8.50 g, 28.7 mmol, 90%). TLC Rf=0.33 (10% EtOAc/Hex) 1HNMR (600 MHz): δ 4.55-4.61 (1H), 3.84-3.91 (m, 1H), 3.70-3.78 (m plus ovlp. s, 4H), 3.47-3.54 (m, 1H), 3.39 (dt, 1H, J1=9.6 Hz, J2=6.7 Hz), 2.33 (t, 2H, J=7.1 Hz), 1.80-1.89 (1H), 1.68-1.76 (1H), 1.50-1.63 (8H), 1.28-1.44 (8H); 13CNMR (150 MHz): δ 154.3, 98.9, 89.9, 72.9, 67.6, 62.3, 52.5, 30.8, 29.7, 29.2, 28.9, 28.7, 27.5, 26.2, 25.5, 19.7, 18.6; FTIR: 2932, 2856, 2236, 1714, 1434, 1249, 1075, 1023, 752 cm−1; HRMS-ESI: calc. for C17H28NaO4 (M+Na)+: 319.1885. found: 319.1887.

Workup

  1. additionwere added dropwise over 5 min
  2. stirringThe reaction was stirred for 30 min at −78° C.
  3. temperaturewarmed to rt over 1 h
  4. customquenched dropwise with H2O (40 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with Et2O (2×25 mL)
  7. dry with materialThe combined organic layers were dried with Na2SO4
  8. customevaporated in vacuo
  9. custompurified by flash column chromatography (step gradient, 5% EtOAc/Hex to 10% EtOAc/Hex)

Sources & evidence

ORD record
ord-7d35e3bb74e243dfa3c3cad45dbe6f3e
Source dataset
uspto-grants-2015_07
Patent number
US09079835B2

Reaction notes

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