Potassium Phosphate, Tribasic → HCID 117982164, compound

HRID 1776093Notes

Reaction equation

HRID 1776093 reaction equation
C12BC(CCC1)CCC2.[CH:10]1([CH2:13][O:14][C@@H:15]([C@@H:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[CH3:28])[C@H:16]([CH:25]=[CH2:26])[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br/[CH:48]=[C:49](\[NH:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])/[C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51]>C1COCC1.CN(C=O)C.CCOCC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:64]([O:63][C:61]([NH:60]/[C:49](=[CH:48]\[CH2:26][CH2:25][C@H:16]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[C@@H:15]([O:14][CH2:13][CH:10]1[CH2:11][CH2:12]1)[C@@H:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)[CH3:28])/[C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])=[O:62])([CH3:67])([CH3:66])[CH3:65]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 117974423HCID 117974423, compoundHCID 131734628HCID 131734628, compound

Product 1

HCID 117982164HCID 117982164, compoundYield 88%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 0.5 M solution of 9-borabicyclo[3.3.1]nonane in anhydrous THF (7.0 mL, 3.50 mmol) was added to a solution of 1-((2S,3R,4S)-3-(cyclopropylmethoxy)-4-((4-methoxybenzyl)oxy)-2-vinylpentyl)-4-fluorobenzene (960 milligrams (mg), 2.409 mmol) in anhydrous THF (5 mL) at 0° C. The resulting solution was warmed to room temperature and stirred for 1 h, then heated to 50° C. for 2 h. The reaction was cooled to room temperature, a solution of K3PO4 (3 M aqueous, 1.61 mL, 4.82 mmol) was added, and the reaction was stirred for 15 min at room temperature. To the mixture was added a solution of (Z)-benzyl 3-bromo-2-((tert-butoxycarbonyl)amino)acrylate (870 mg, 2.44 mmol), prepared using a similar procedure to that disclosed in Singh, J. et al. Org. Lett. 2003, 5, 3155-3158, in degassed DMF (2 mL) and PdCl2(dppf) (88.0 mg, 0.120 mmol). The reaction was heated overnight at 60° C., cooled, diluted with Et2O, and washed with saturated aqueous NaHCO3. The phases were separated and the aqueous phase was extracted with Et2O. The combined organic phases were washed with saturated aqueous NH4Cl and water, dried over MgSO4, concentrated, and purified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate) to furnish the title product as a pale yellow oil (1.43 g, 88%): 1H NMR (400 MHz, CDCl3) δ 7.38-7.26 (m, 5H), 7.26-7.19 (m, 2H), 6.97-6.89 (m, 2H), 6.88-6.78 (m, 4H), 6.39 (t, J=7.2 Hz, 1H), 6.29 (s, 1H), 5.24-5.10 (m, 2H), 4.61-4.25 (m, 2H), 3.73 (s, 3H), 3.64-3.53 (m, 1H), 3.45-3.31 (m, 2H), 3.22 (dd, J=7.2, 2.8 Hz, 1H), 2.79 (dd, J=14.0, 4.8 Hz, 1H), 2.37 (dd, J=14.0, 9.5 Hz, 1H), 2.25-2.08 (m, 2H), 1.92-1.79 (m, 1H), 1.57-1.43 (m, 1H), 1.43 (s, 9H), 1.39-1.28 (m, 1H), 1.28 (d, J=6.0 Hz, 3H), 1.09-0.96 (m, 1H), 0.53-0.44 (m, 2H), 0.21-0.13 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 164.48, 160.91 (d, J=243.2 Hz), 158.99, 153.40, 136.94 (d, J=3.2 Hz), 136.82, 135.55, 130.26, 130.24 (d, J=7.7 Hz), 129.39, 128.31, 128.04, 128.00, 126.23, 114.62 (d, J=20.9 Hz), 113.58, 82.58, 80.01, 76.69, 74.41, 69.70, 66.72, 54.94, 40.81, 34.83, 28.49, 27.99, 25.75, 16.00, 11.01, 2.86, 2.78; 19F NMR (376 MHz, CDCl3) δ −117.70; ESIMS m/z 676.4 ([M+H]+).

Workup

  1. temperatureheated to 50° C. for 2 h
  2. temperatureThe reaction was cooled to room temperature
  3. stirringthe reaction was stirred for 15 min at room temperature
  4. customprepared
  5. temperatureThe reaction was heated overnight at 60° C.
  6. temperaturecooled
  7. washwashed with saturated aqueous NaHCO3
  8. customThe phases were separated
  9. extractionthe aqueous phase was extracted with Et2O
  10. washThe combined organic phases were washed with saturated aqueous NH4Cl and water
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated
  13. custompurified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-10ee741f3d9d4926849c545baf34c0c5
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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