Potassium Carbonate → HCID 69001267, compound

HRID 1879235Notes

Reaction equation

HRID 1879235 reaction equation
[CH2:1]([N:4]([S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1)(=[O:22])=[O:21])[C@@H:5]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C:6]([CH3:9])([CH3:8])[CH3:7])[CH:2]=[CH2:3].B1C2CCCC1CCC2.Br[C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CN(C=O)C.C(OCC)(=O)C.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.O>[CH2:13]([O:12][C:10](=[O:11])[C@H:5]([N:4]([S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1)(=[O:22])=[O:21])[CH2:1][CH2:2][CH2:3][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1)[C:6]([CH3:9])([CH3:8])[CH3:7])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 122863-BromopyridineHCID 789669-Borabicyclo(3.3.1)nonaneHCID 68999085HCID 68999085, compound

Product 1

HCID 69001267HCID 69001267, compoundYield 59%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl N-allyl-N-[(3-methoxyphenyl)sulfonyl]-3-methyl-D-valinate (222.6 mg, 0.5 mmol) in THF (1 mL) cooled to 0° C. is slowly added a 0.5M solution of 9-BBN (3.0 mL, 1.50 mmol) in THF. The mixture is slowly warmed to room temperature and stirred for two days. This solution is then added to a separate flask containing 3-bromopyridine, Pd(PPh3)4 (57.7 mg, 0.05 mmol), and potassium carbonate (276.2 mg, 2 mmol) in DMF (3.3 mL). The resulting mixture is heated to 70° C. and stirred overnight. The reaction is diluted with ethyl acetate and poured into water. The aqueous layer is extracted three times with ethyl acetate, and the combined organic extracts are washed with brine, dried with sodium sulfate, and concentrated. The crude residue is purified by column chrornotagraphy eluting with a gradient of 15-100% ethyl acetate in heptane to yield the desired product as a clear oil (130 mg, 59%). 1H NMR (CDCl3, 400 MHz); δ 8.48 (d, 1H, J=4), 8.43 (s, 1H), 7.58 (d, 1H, J=8), 7.35-7.33 (m, 3H), 7.29-7.27 (m, 1.5H), 7.25-7.23 (m, 1.5H), 7.19-7.18 (m, 2H), 7.05-7.03 (d, 1H, J=8), 4.87 (d, 1H, J=12), 4.69-4.66 (d, 1H, J=12H), 4.36 (s, 1H), 3.74 (s, 3H), 3.57 (m, 1H), 3.18 (m, 1H), 2.58 (t, 2H, J=4), 2.41 (m, 1H), 2.05 (m, 1H), 1.05 (s, 9H). Mass spectrum (511.5; M+1).

Workup

  1. additionThis solution is then added to a separate flask
  2. temperatureThe resulting mixture is heated to 70° C.
  3. stirringstirred overnight
  4. extractionThe aqueous layer is extracted three times with ethyl acetate
  5. washthe combined organic extracts are washed with brine
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated
  8. customThe crude residue is purified by column chrornotagraphy
  9. washeluting with a gradient of 15-100% ethyl acetate in heptane

Sources & evidence

ORD record
ord-9041d95424b14adbb2f19cbcead79e0a
Source dataset
uspto-grants-2012_11
Patent number
US08314148B2

Reaction notes

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