Ethyl Acetate → 4-Fluoro-N-((6S,9S,12S)-6-formyl-9-isopropyl-8,11-dioxo-2-oxa-7,10-diaza-bicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)-benzenesulfonamide

HRID 58393Notes

Reaction equation

HRID 58393 reaction equation
C[O:2][C:3]([C@H:5]1[NH:20][C:19](=[O:21])[C@H:18]([CH:22]([CH3:24])[CH3:23])[NH:17][C:16](=[O:25])[C@@H:15]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH2:14][C:13]2=[CH:37][CH:38]=[C:10]([CH:11]=[CH:12]2)[O:9][CH2:8][CH2:7][CH2:6]1)=O.CC(C[AlH]CC(C)C)C.CCOC(C)=O>C(Cl)Cl>[F:36][C:33]1[CH:34]=[CH:35][C:30]([S:27]([NH:26][C@H:15]2[CH2:14][C:13]3=[CH:12][CH:11]=[C:10]([CH:38]=[CH:37]3)[O:9][CH2:8][CH2:7][CH2:6][C@@H:5]([CH:3]=[O:2])[NH:20][C:19](=[O:21])[C@H:18]([CH:22]([CH3:23])[CH3:24])[NH:17][C:16]2=[O:25])(=[O:28])=[O:29])=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydrideHCID 66846973HCID 66846973, compound

Product 1

HCID 573915034-Fluoro-N-((6S,9S,12S)-6-formyl-9-isopropyl-8,11-dioxo-2-oxa-7,10-diaza-bicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)-benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Ester 68 (39 mg) was dissolved in DCM (6 mL) under an atmosphere of argon. The reaction was cooled to −78° C. To the resultant solution DIBAL (0.39 mL) was added dropwise. This was stirred for 2 h before being allowed to warm to rt overnight. The reaction mixture was partitioned between EtOAc and 1M hydrochloric acid. The aqueous phase was extracted again with EtOAc and the combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. Purification was achieved using flash chromatography, eluting with a gradient of 1/1 EtOAc/(50/70) petroleum ether to EtOAc to yield a light brown solid, 15 mg, 40%. Rf=0.25 (1/1 EtOAc/(50/70) petroleum ether).

Workup

  1. temperatureto warm to rt overnight
  2. customThe reaction mixture was partitioned between EtOAc and 1M hydrochloric acid
  3. extractionThe aqueous phase was extracted again with EtOAc
  4. dry with materialthe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification
  8. washeluting with a gradient of 1/1 EtOAc/(50/70) petroleum ether to EtOAc
  9. customto yield a light brown solid, 15 mg, 40%

Sources & evidence

ORD record
ord-94286a6b253548a0959ead3e1de72680
Source dataset
uspto-grants-2016_09
Patent number
US09434762B2

Reaction notes

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