Citric Acid → 1-Trityloxymethyl-cyclopropanol

HRID 1714492Notes

Reaction equation

HRID 1714492 reaction equation
C([O:3][C:4](=O)[CH2:5][O:6][C:7]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)(C1C=CC=CC=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)C.[CH2:27]([Mg]Br)[CH3:28].[C:31](O)(=O)[CH2:32][C:33]([CH2:38][C:39](O)=O)(C(O)=O)O.O1CCC[CH2:45]1>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[C:7]([O:6][CH2:5][C:4]1([OH:3])[CH2:28][CH2:27]1)([C:31]1[CH:32]=[CH:33][CH:38]=[CH:39][CH:45]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 8028TetrahydrofuranHCID 12230788trityloxy-acetic Acid Ethyl Ester3×HCID 178418443HCID 178418443, compound

Product 1

HCID 115807541-Trityloxymethyl-cyclopropanol

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Conditions

Temperature
0 °C

Procedure

Tetrahydrofuran [1040 ml, 3 ml/g with respect to the compound of formula (8)] was added to the compound of formula (8) prepared in Example 1 on the premise that the yield of Example 1 is 100%, and the mixture was cooled to 0° C. Titanium tetraisopropoxide (113.8 g, 0.4 mol) was added thereto, and ethyl magnesium bromide (1500 ml, 3.0 mol, 1 M concentration) was added thereto dropwise at 5˜15° C. over 3˜6 hours. After completion of the reaction was confirmed by HPLC, 20% aqueous citric acid solution [1790 ml, 5 ml/g with respect to the compound of formula (8)] was added to the reaction solution under the condition of not exceeding 35° C., which was stirred for about 1 hour. After the stirring, tetrahydrofuran therein was distilled under reduced pressure, and the residue was extracted twice, first with 1390 ml [4 ml/g with respect to the compound of formula (8)] of ethyl acetate and second with 690 ml [2 ml/g with respect to the compound of formula (8)] of the same. Thus resulted organic layer was washed with saturated aqueous NaHCO3 solution [690 ml, 2 ml/g with respect to the compound of formula (8)], and concentrated under reduced pressure to give the title compound of formula (9).

Workup

  1. waitdropwise at 5˜15° C. over 3˜6 hours
  2. additionwas added to the reaction solution under the condition of not
  3. customexceeding 35° C.
  4. distillationAfter the stirring, tetrahydrofuran therein was distilled under reduced pressure
  5. extractionthe residue was extracted twice, first with 1390 ml [4 ml/g with respect to the compound of formula (8)] of ethyl acetate
  6. washThus resulted organic layer was washed with saturated aqueous NaHCO3 solution [690 ml, 2 ml/g with respect to the compound of formula (8)], and
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e03cd99c59a347a8856ad51ed0106773
Source dataset
uspto-grants-2010_09
Patent number
US07795463B2

Reaction notes

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