Ethyl 6-bromohexanoate → Ethyl 17-(tetrahydropyran-2-yl-oxy)-heptadecanoate

HRID 1367723Notes

Reaction equation

HRID 1367723 reaction equation
I[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1.Br[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27].CC([C@@H]1N=C(C2C=CC=C(C3OC[C@H](C(C)C)N=3)N=2)OC1)C>CC([C@H]1N=C(C2C=CC=C(C3OC[C@@H](C(C)C)N=3)N=2)OC1)C.CC(N(C)C)=O.[Zn].Cl[Ni]Cl.C(COC)OC.IC1C=CC(CCCCCCCCCCCCCCCCCCO)=CC=1>[O:15]1[CH2:16][CH2:17][CH2:18][CH2:19][CH:14]1[O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]

Participants

9

Reactant 3

HCID 117544Ethyl 6-bromohexanoateHCID 558999Tetrahydropyran, 2-(11-iodoundecyloxy)-2×HCID 688211(S,S)-2,6-Bis(4-isopropyl-2-oxazolin-2-yl)pyridine

Product 1

HCID 66970149Ethyl 17-(tetrahydropyran-2-yl-oxy)-heptadecanoateYield 95%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 1165580418-(p-Iodophenyl)octadecanolCatalystHCID 15773433Dichloronickel;1,2-dimethoxyethaneCatalystHCID 31374DimethylacetamideSolvent3×HCID 688213(R,R)-2,6-Bis(4-isopropyl-2-oxazolin-2-yl)pyridineSolvent

Conditions

Temperature
0 °C

Procedure

From (77) and (36). Zinc powder (342 mg, 5.27 mmol) was dried at 70° C. for 30 min in a sealed tube, then DMA (2 ml) and solid 12 (45 mg, 0.18 mmol) were added. After stirring for 10 min, neat ethyl 6-bromohexanoate (0.63 ml, 3.52 mmol) was added and the reaction mixture was stirred in the sealed tube for 10 h at 75° C. In a 10-ml flask, NiCl2-glyme (52 mg, 0.23 mmol) and (R)-(i-Pr)-Pybox (or (S)-(i-Pr)-Pybox) (92 mg, 0.31 mmol) were dissolved in DMA (1.5 ml), cooled to 0° C. and solution of I(CH2)11OTHP 77 (896 mg, 2.34 mmol) in DMA (0.5 ml) was added. Then the solution of organozinc reagent 36 was added. The reaction mixture was stirred at 0° C. for 6 h and at room temperature for 6 h, then quenched by addition of aqueous NH4Cl, extracted with EtOAc, extract was dried over Na2SO4 and evaporated. The crude product was purified as in Method 1 to give compound 78 (888 mg, 95%).

Workup

  1. stirringthe reaction mixture was stirred in the sealed tube for 10 h at 75° C
  2. stirringThe reaction mixture was stirred at 0° C. for 6 h and at room temperature for 6 h
  3. customquenched by addition of aqueous NH4Cl
  4. extractionextracted with EtOAc
  5. extractionextract
  6. dry with materialwas dried over Na2SO4
  7. customevaporated
  8. customThe crude product was purified as in Method 1

Sources & evidence

ORD record
ord-7e663649b5854a36b5a4de9c6acbe9d5
Source dataset
uspto-grants-2011_02
Patent number
US07893286B2

Reaction notes

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