Trimethyl borate → HCID 23072394, compound

HRID 1182493Notes

Reaction equation

HRID 1182493 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[Li]CCCC.B(OC)(OC)OC.Br[C:21]1[CH:39]=[CH:38][C:24]([C:25]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:26])=[CH:23][CH:22]=1>C(OCC)C.C1COCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:36]([O:35][C:33](=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][C:25](=[O:26])[C:24]1[CH:23]=[CH:22][C:21]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[CH:39][CH:38]=1)[CH3:37]

Participants

9

Reactant 4

HCID 8470Trimethyl borateHCID 122863-BromopyridineHCID 11024292ETHYL 8-(4-BROMOPHENYL)-8-OXOOCTANOATEHCID 178418339Butyllithium

Product 1

HCID 23072394HCID 23072394, compoundYield 25.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-bromopyridine (728 mg, 4.6 mmol) in dry diethyl ether (9 mL) at −78° C. was added n-BuLi (2.5M solution in hexane, 1.8 mL, 4.5 mmol). The reaction mixture was stirred for 20 minutes at 0° C. After a dropwise addition of trimethyl borate (0.5 mL, 4.5 mmol) the mixture was stirred for 1 hour at 0° C. and then a solution of bromoester 49d (1.02 g, 3 mmol) in THF (9 mL) and water (2.3 mL) containing Pd(PPh3)4 (278 mg, 8 mol %, 0.27 mmol) was added. The reaction mixture was refluxed at 70° C. for 24 hours, cooled to room temperature, filtered through a pad of Celite and rinsed with ethyl acetate. The solution was extracted with ethyl acetate (2×30 mL), washed with brine (10 mL), dried (MgSO4) and concentrated. Purification by flash silica gel chromatography (1% methanol in dichloromethane) afforded the corresponding ester 125 (259 mg, 25% yield) as a white solid. MS (ESI)=340 (MH+).

Workup

  1. stirringwas stirred for 1 hour at 0° C.
  2. additionwas added
  3. temperatureThe reaction mixture was refluxed at 70° C. for 24 hours
  4. temperaturecooled to room temperature
  5. filtrationfiltered through a pad of Celite
  6. washrinsed with ethyl acetate
  7. extractionThe solution was extracted with ethyl acetate (2×30 mL)
  8. washwashed with brine (10 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customPurification by flash silica gel chromatography (1% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b08696519f7742b1969f94c9d43f7b91
Source dataset
uspto-grants-2007_10
Patent number
US07288567B2

Reaction notes

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