Diethanolamine → Ethyl 2-(3-(3-((2-tetrahydropyranyl)oxymethyl)phenyl)-3(S)-hydroxypropyl)benzoat

HRID 1720361Notes

Reaction equation

HRID 1720361 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][C:9]1[CH:10]=[C:11]([C:15](=[O:29])[CH2:16][CH2:17][C:18]2[CH:28]=[CH:27][CH:26]=[CH:25][C:19]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:12]=[CH:13][CH:14]=1.CB1N2CCCC2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.B.B.C1COCC1.N(CCO)CCO>C1COCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][C:9]1[CH:10]=[C:11]([C@@H:15]([OH:29])[CH2:16][CH2:17][C:18]2[CH:28]=[CH:27][CH:26]=[CH:25][C:19]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 8113DiethanolamineHCID 2723981Borane;tetrahydrofuranHCID 22417658Ethyl 2-(3-(3-(((2-tetrahydropyranyl)oxy)methyl)phenyl)-3-oxopropyl)benzoateHCID 178419159HCID 178419159, compound

Product 1

HCID 22859882Ethyl 2-(3-(3-((2-tetrahydropyranyl)oxymethyl)phenyl)-3(S)-hydroxypropyl)benzoatYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-45 °C

Procedure

The keto ester of Step 13 (24.8 g, 62.5 mmol) was dissolved in THF (230 mL) and cooled to -45° C. A THF (15 mL) solution of tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole-borane adduct (J. Org. Chem., 56, 751 (1991), 4.55 g, 15.6 mmol) was added dropwise and the resulting mixture was stirred 20 minutes at -45° C. To this solution, 1.0M borane-THF (62.5 mL, 62.5 mmol) was added dropwise over 30 minutes. The reaction mixture was stirred 1 hour at -45° C. followed by another 2 hours with slow warming to -20° C. After cooling the solution of -40° C., it was poured onto 25% aq. NH4OAC (425 mL) and 1.0M diethanolamine (40 mL) at 0° C. and stirred vigorously for 20 minutes. The title compound was extracted with EtOAc (3×), dried over MgSO4 and concentrated under reduced pressure. The crude oil was purified by flash chromatography (25% to 50% EtOAc in hexanes) to yield 22.6 g (91%) of the desired product as an oil.

Workup

  1. stirringThe reaction mixture was stirred 1 hour at -45° C.
  2. waitfollowed by another 2 hours
  3. temperaturewith slow warming to -20° C
  4. temperatureAfter cooling the solution of -40° C., it
  5. stirringstirred vigorously for 20 minutes
  6. extractionThe title compound was extracted with EtOAc (3×)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude oil was purified by flash chromatography (25% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b7403597237b41ffa710b2c5e0817c33
Source dataset
uspto-grants-1996_04
Patent number
US05506227

Reaction notes

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