Water → HCID 118207360, compound

HRID 1507274Notes

Reaction equation

HRID 1507274 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[F:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])(C)C)=[O:32])[CH2:27][CH:26]=2)O1.O.C([O-])([O-])=O.[Na+].[Na+].[C:46](#N)[CH3:47]>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>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][CH2:34][CH2:37][CH2:46][CH3:47])=[O:32])[CH2:27][CH:26]=2)=[CH:11][C:10]=1[F:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 187574911-(Benzyloxy)-4-bromo-2-fluorobenzene

Product 1

HCID 118207360HCID 118207360, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (5.0 g, 17.8 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (6.60 g, 21.3 mmol) in acetonitrile (50 mL) was degassed for 5 min. To this was added water (50 mL), Na2CO3 (5.66 g, 53.4 mmol) and Pd(Ph3P)4 (1.23 g, 1.07 mmol) and the reaction was further degassed for 10 min. It was then heated to 80° C. for 16 h. The reaction cooled to rt, poured into water, and extracted with EtOAc. The combined organic layers were, dried with magnesium sulfate, filtered through celite, and concentrated in vacuo to afford a brown oil. The oil was purified using silica gel column chromatography (0-30% EtOAc/hexanes) to afford 1-butyl 4-(4-(benzyloxy)-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate (5.63 g, 83% yield): LC-MS [M+H]+−tBu+ACN=369.2; 1H NMR (500 MHz, DMSO-d6) δ 7.51-7.27 (m, 6H), 7.25-7.13 (m, 2H), 6.12 (br. s., 1H), 5.19 (s, 2H), 3.97 (br. s., 2H), 3.51 (t, J=5.6 Hz, 2H), 2.41 (d, J=1.5 Hz, 2H), 1.42 (s, 9H).

Workup

  1. customthe reaction was further degassed for 10 min
  2. temperatureThe reaction cooled to rt
  3. additionpoured into water
  4. extractionextracted with EtOAc
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered through celite
  7. concentrationconcentrated in vacuo
  8. customto afford a brown oil
  9. customThe oil was purified

Sources & evidence

ORD record
ord-3b13802e2cd84257903c27dd523b452e
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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