Diisobutylaluminum hydride → E-N-[3-(5-(4-Fluorophenylmethyl)-thien-2-yl)-1-(R)-methyl-2-propenyl]-N-hydroxyurea

HRID 1720437Notes

Reaction equation

HRID 1720437 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[S:13][C:12]([C:14]#[C:15][C@H:16]([N:18]([OH:22])[C:19]([NH2:21])=[O:20])[CH3:17])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.CC(C[AlH]CC(C)C)C>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[S:13][C:12](/[CH:14]=[CH:15]/[C@H:16]([N:18]([OH:22])[C:19]([NH2:21])=[O:20])[CH3:17])=[CH:11][CH:10]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 3086671Atreleuton

Product 1

HCID 22860091E-N-[3-(5-(4-Fluorophenylmethyl)-thien-2-yl)-1-(R)-methyl-2-propenyl]-N-hydroxyureaYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea (0.316g, 1.05 mmol), prepared as in Example 1, step 4, in THF (8 mL) at -70° C. was added DIBAL (5.23 mL, 5.25 mmol). The reaction was slowly allowed to warm to ambient temperature over 17 hours. The reaction was quenched into an aqueous 1M H3PO4 solution and extracted with ethyl acetate. The combined organic layers were washed with aqueous NaHCO3, dried (MgSO4) and evaporated. The residue was purified by chromatography on silica gel (50% ethyl acetate/hexanes/1% acetic acid). The resulting solid was crystallized from hot ethyl acetate/hexanes to yield 0.063 g (20% ) of E-N-[3-(5-(4-Fluorophenylmethyl)-thien-2-yl)-1-(R)-methyl-2-propenyl]-N-hydroxyurea. m.p. 143°-4° C). MS (DCI/NH3) m/e 321 (M+H)+, 338 (M+NH4)+. 1H NMR (DMSO-d6, 300 MHz) δ1.17(d, J=7.2 Hz, 3H), 4.08 (s, 2H), 4.73 (m, 1H), 5.88 (dd, J=6.3, 15.6 Hz, 1H), 6.33 (s, 2H), 6.55 (d, J=15.6 Hz, 1H), 6.77 (d, J=4.2 Hz, 1H), 6.83 (d, J=4.2 Hz, 1H), 7.12 (m, 2H), 7.29 (m, 2H), 9.02 (s, 1H). Anal Calcd for C17H17FN2O2S: C, 59.98; H, 5.35; N, 8.74. Found C, 60.15; H, 5.11; N, 8.75.

Workup

  1. customThe reaction was quenched into an aqueous 1M H3PO4 solution
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with aqueous NaHCO3
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by chromatography on silica gel (50% ethyl acetate/hexanes/1% acetic acid)
  7. customThe resulting solid was crystallized from hot ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1ec20c48c35943dfb53959b8ca8a902f
Source dataset
uspto-grants-1996_04
Patent number
US05506261

Reaction notes

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