Sodium cyanoborohydride → 1-[(6-Fluoro-1-benzothien-3-yl)methyl]-3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine

HRID 10221

Reaktionsgleichung

Reaktionsgleichung von HRID 10221
C([BH3-])#N.[Na+].Cl.[F:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH2:16][CH:17]2[CH2:20][NH:19][CH2:18]2)(=[O:15])=[O:14])=[CH:9][CH:8]=1.[F:21][C:22]1[CH:32]=[CH:31][C:25]2[C:26]([CH:29]=O)=[CH:27][S:28][C:24]=2[CH:23]=1>CO.C(O)(=O)C>[F:21][C:22]1[CH:32]=[CH:31][C:25]2[C:26]([CH2:29][N:19]3[CH2:20][CH:17]([CH2:16][S:13]([C:10]4[CH:11]=[CH:12][C:7]([F:6])=[CH:8][CH:9]=4)(=[O:15])=[O:14])[CH2:18]3)=[CH:27][S:28][C:24]=2[CH:23]=1

Komponenten

6

Edukt 3

HCID 5003444Sodium cyanoborohydrideHCID 219783933-{[(4-Fluorophenyl)sulfonyl]methyl}azetidine hydrochlorideHCID 823742096-Fluoro-1-benzothiophene-3-carbaldehyde

Produkt 1

HCID 219784271-[(6-Fluoro-1-benzothien-3-yl)methyl]-3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittel

Versuchsvorschrift

Sodium cyanoborohydride (13 mg, 0.20 mmol) was added to a stirred solution of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (Example 1 Step 4, 49 mg, 0.18 mmol) and 6-fluoro-1-benzothiophene-3-carbaldehyde (36 mg, 0.20 mmol) in methanol (3 mL) and acetic acid (50 μL). The reaction was stirred at room temperature for 4 hours. The solvent was removed in vacuo and the residue partitioned between sodium carbonate and ethyl acetate. The aqueous layer was extracted with further ethyl acetate and the combined organic layers washed with water and brine, dried over MgSO4 and evaporated. The residue was purified by preparative TLC (40% ethyl acetate/isohexane) to give the title compound which was treated with ethereal HCl to give the hydrochloride salt (46 mg, 59%). 1H NMR (400 MHz, CD3OD) δ 8.00–7.96 (3H, m), 7.88 (1H, s), 7.74 (1H, dd, J=2.4, 8.8 Hz), 7.43–7.37 (2H, m), 7.31–7.27 (1H, m), 4.68 (2H, s), 4.24 (2H, s), 4.16 (2H, t, J=9.7 Hz), 3.67 (2H, d, J=7.6 Hz), 3.30–3.22 (1H, m); m/z (ES+) 394 (M+H)+.

Aufarbeitung

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between sodium carbonate and ethyl acetate
  3. extractionThe aqueous layer was extracted with further ethyl acetate
  4. washthe combined organic layers washed with water and brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe residue was purified by preparative TLC (40% ethyl acetate/isohexane)

Quellen und Nachweise

ORD-Eintrag
ord-f183d92f09df40309c2cbbef87d5eb4a
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07094777B2

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