Hydrochloric Acid → HCID 11126489, compound

HRID 536773Notes

Reaction equation

HRID 536773 reaction equation
C1(C)C=CC=CC=1.[CH3:8][Si:9]([CH3:17])([CH3:16])[C:10]#[C:11][C:12](=[O:15])[CH:13]=[CH2:14].CO.Cl>C1COCC1.C(OCC)C>[CH3:8][Si:9]([CH3:17])([CH3:16])[C:10]#[C:11][C@H:12]([OH:15])[CH:13]=[CH2:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887Methanol2×HCID 1140TolueneHCID 11332572HCID 11332572, compound

Product 1

HCID 11126489HCID 11126489, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R)-Me-CBS reagent (1.0 M Toluene, 2.14 mL, 2.14 mmol) was transferred into a freshly flame-dried flask, and the toluene was removed in vacuo over 1 day. The CBS reagent was diluted with a THF solution of 5-trimethylsilyl-1-penten-4-yn-3-one (163 mg, 1.07 mmol), and the resultant solution was cooled to −30° C. At −30° C., BH3-Me2S (0.589 mL, 1.18 mmol) was slowly added over 10 min. After addition of BH3-Me2S, TLC analyses indicated that the reaction was complete. Methanol was slowly added, and reaction mixture was slowly warmed to room temperature. The reaction mixture was diluted with diethyl ether, and the resultant organic phase was washed with 2:1 (v:v) NaOH/saturated NaHCO3 solution until the aqueous phase was clear, and then washed with brine. After being dried over MgSO4, the organic phase was removed, diluted with diethyl ether, and to this was added a solution of 0.5 M HCl in methanol (4.5 mL, 2.14 mmol). Precipitates were removed by filtration. The crude product in the solvent mixture was purified by flash column chromatography (hexane/ether 5:1) to provide (3R)-5-trimethylsilyl-1-penten-4-yn-3-ol (0.163 g, 100% yield) as a colorless oil: Rf: 0.4 (hexane/dichloromethane 2:1); [α]D20.0°: −24.1 (c=1, CHCl3); 1H NMR (400 MHz, CDCl3): δ 5.95 (ddd, 1H, J=17.0, 10.1, 5.29 Hz), 5.46 (d, 1H, J=7.0 Hz), 5.21 (d, 1H, J=10.1 Hz), 4.86 (d, 1H, J=3.87 Hz), 2.17 (br s, 1H), 0.16 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 137.0, 116.8, 104.9, 91.3, 63.9, 0.2; IR (neat) v: 3368.7, 2961.3, 2927.0, 2855.3, 2174.4, 1250.9, 843.7 cm−1; HRMS: calculated 154.28, found 154.0817 for [M]+.

Workup

  1. customthe toluene was removed in vacuo over 1 day
  2. customreaction mixture
  3. washthe resultant organic phase was washed with 2:1 (v:v) NaOH/saturated NaHCO3 solution until the aqueous phase
  4. washwashed with brine
  5. dry with materialAfter being dried over MgSO4
  6. customthe organic phase was removed
  7. additiondiluted with diethyl ether
  8. customPrecipitates
  9. customwere removed by filtration
  10. customThe crude product in the solvent mixture was purified by flash column chromatography (hexane/ether 5:1)

Sources & evidence

ORD record
ord-048169497b964e9ea48d6138d55bf257
Source dataset
uspto-grants-2014_10
Patent number
US08859615B2

Reaction notes

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