Tetrahydrofuran → HCID 11664199, compound

HRID 1993979Notes

Reaction equation

HRID 1993979 reaction equation
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:30][CH2:29][C@@H:19]3[CH2:20][N:21]([C:23]4[CH2:27][CH2:26][C:25](=[O:28])[CH:24]=4)[CH2:22][C@H:18]3[C@@H:17]2[C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Li+].CC([N-]C(C)C)C.C1C[O:51]CC1>>[F:39][C:2]([F:1])([F:38])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:30][CH2:29][C@@H:19]3[CH2:20][N:21]([C:23]4[CH2:27][CH:26]([OH:51])[C:25](=[O:28])[CH:24]=4)[CH2:22][C@H:18]3[C@@H:17]2[C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2724682Lithium diisopropylamideHCID 11512394HCID 11512394, compound

Product 1

HCID 11664199HCID 11664199, compound

Conditions

Temperature
-78 °C

Procedure

To a solution of 20 mg (0.0359 mmol) of 3-[(3aS,6R,7R,7aR)-6-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluorophenyl)hexahydropyrano[3,4-c]pyrrol-2(3H)-yl]cyclopent-2-en-1-one (example 3) and 19 mg (0.0430 mmol) MoOPH in 1.0 mL dry THF under nitrogen atmosphere at −78° C. was added 0.045 mL (0.15 mmol) of 2.0 M solution of LDA. The resulting mixture was stirred at −78° C. for 1 hr then quenched by the addition of sat. aq. Na2S2O3. The mixture was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4 and filtered through a fritted funnel. The residue was purified by prep TLC eluting with 95/5 DCM/(10% NH4OH/methanol) to afford the title compound as a mixture of diastereomers. 1H-NMR (CD3OD): δ: 1.38 (d, 3H, J=6.5 Hz), 2.15-2.50 (m, 3H), 2.60-2.82 (m, 1H), 2.90-3.22 (m, 4H), 3.40-3.86 (m, 2H), 4.14-4.24 (m, 1H), 4.25-4.32 (m, 1H), 4.38-4.44 (m, 1H), 4.73-4.85 (m, 1H), 4.09 (q, 1H, J=6.5 Hz), 6.60-7.12 (m, 2H), 7.16-7.22 (m, 2H), 7.38 (s, 2H), 7.76 (s, 1H) ppm. MS: (MH)+574.

Workup

  1. customthen quenched by the addition of sat. aq. Na2S2O3
  2. extractionThe mixture was extracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered through a fritted funnel
  6. customThe residue was purified by prep TLC
  7. washeluting with 95/5 DCM/(10% NH4OH/methanol)

Sources & evidence

ORD record
ord-275267638c8a414fb357bd65ea0d957d
Source dataset
uspto-grants-2010_01
Patent number
US07652058B2

Reaction notes

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