Tetrahydrofuran → HCID 68701713, compound

HRID 2118402Notes

Reaction equation

HRID 2118402 reaction equation
C([C@H]1C[C@H:6]2[C@@H:7]([C:16]3[CH:21]=[CH:20][C:19](O)=[CH:18][CH:17]=3)[O:8][C:9]3C=CC(O)=CC=3[C@H]2C1)C.C[Si]([N-][Si](C)(C)C)(C)C.[K+].CN(C)P(N(C)C)(N(C)C)=O.COC1CC2[CH:51]([C:63]3[CH:68]=[CH:67][C:66](OCOC)=[CH:65][CH:64]=3)[O:52][C:53]3[CH:54]=[CH:55][C:56]([O:59][CH2:60][O:61]C)=[CH:57][C:58]=3C2C1.C1C[O:77][CH2:76]C1>>[CH2:19]([CH:20]1[C:57]2[C:56](=[CH:55][CH:54]=[C:53]([O:52][CH2:51][C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[CH:58]=2)[O:59][C:60](=[O:61])[CH:21]1[CH2:16][C:7]([O:8][CH2:9][O:77][CH3:76])=[CH2:6])[CH:18]=[CH2:17]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 12679HexamethylphosphoramideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 11472382HCID 11472382, compoundHCID 68703551HCID 68703551, compound

Product 1

HCID 68701713HCID 68701713, compound

Procedure

Cool a solution of Preparation 39 (3.65 g, 12.4 mmol) in THF (90 mL) to −78 C. Add a solution of KHMDS (32 mL, 0.5 M in toluene, 16 mmoL) over 5 min, then allow to stir for 15 in at −78 C. Add hexamethylphosphoramide (HMPA) via syringe (2.8 mL, 16.1 mmoL) quickly, and allow to stir for 20 min at −78 C. Add 2-O-methoxylmethyl allyl iodide (4.24 g) over 2 min, and then allow the solution to warm to −50 C. over 1.5 h. Pour the contents of the reaction into ½ satd. NaHCO3 and extract with Et2O (2×100 mL) and EtOAc (2×100 mL). Wash the combined organic extracts with H2O (2×150 mL) and brine (150 mL) and then dry over Na2SO4. Concentrate the crude product to leave a brown oil, which is purified by MPLC (0% to 12% to 20% EtOAc/hexanes) to afford Preparation 40 (3.72 g, 76%) as a light yellow oil. 1H NMR (CDCl3) δ 7.31-7.44 (m, 5H), 6.98 (d, J=8.8 Hz, 1H), 6.87 (dd, J=8.8, 3.2 Hz, 1H), 6.74 (d, J=3.2 Hz, 1H), 5.66 (m, 1H), 5.01-5.09 (m, 4H), 4.93 (A ob AB, JAB=6.4 Hz, 1H), 4.90 (B of AB, JAB=6.4 Hz, 1H), 4.18 (d, J=2.4 Hz, 1H), 3.87 (d, J=2.4 Hz, 1H), 3.44 (s, 3H), 3.18 (m, 1H), 2.86 (m, 1H), 2.22-2.39 (m, 3H), 2.12 (dd, J=9.4, 14.0 Hz, 1H).

Workup

  1. temperatureCool
  2. stirringto stir for 20 min at −78 C
  3. temperatureto warm to −50 C
  4. additionPour
  5. customthe contents of the reaction into ½ satd
  6. extractionNaHCO3 and extract with Et2O (2×100 mL) and EtOAc (2×100 mL)
  7. washWash the combined organic extracts with H2O (2×150 mL) and brine (150 mL)
  8. dry with materialdry over Na2SO4
  9. concentrationConcentrate the crude product
  10. customto leave a brown oil, which
  11. customis purified by MPLC (0% to 12% to 20% EtOAc/hexanes)
  12. customto afford

Sources & evidence

ORD record
ord-37bf451035ab453b8f6779ef7eca4a09
Source dataset
uspto-grants-2008_10
Patent number
US07442812B2

Reaction notes

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