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

HRID 10221

Reaction equation

HRID 10221 reaction equation
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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-f183d92f09df40309c2cbbef87d5eb4a
Source dataset
uspto-grants-2006_08
Patent number
US07094777B2

Linked notes

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