Acetic Acid → (3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-1,1-dioxo-tetrahydro-thiophen-3-ylamine

HRID 1169249Notes

Reaction equation

HRID 1169249 reaction equation
[NH2:1][C@@H:2]1[CH2:6][S:5](=[O:8])(=[O:7])[CH2:4][C@H:3]1[C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:12]1)=O.O1CCCC1.C(O)(=O)C>CO>[F:24][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][C@@H:13]2[CH2:14][CH2:15][CH2:16][N:11]([CH2:9][C@@H:3]3[CH2:4][S:5](=[O:7])(=[O:8])[CH2:6][C@H:2]3[NH2:1])[CH2:12]2)=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 69748830[(3R,4S)-4-Amino-1,1-dioxo-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-methanone

Product 1

HCID 69747909(3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-1,1-dioxo-tetrahydro-thiophen-3-ylamineYield 61.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

[(3R,4S)-4-Amino-1,1-dioxo-tetrahydrothiophen-3-yl]-[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-methanone (560 mg, 1.46 mmol) was treated with borane-tetrahydrofuran complex in tetrahydrofuran (1.0 M; 58 mL, 58 mmol) and stirred for 16.5 h . The mixture was treated slowly with 20% acetic acid in methanol (38 mL), and the resulting mixture was stirred at room temperature for 5.5 h . The solvents were removed, and the residue was dissolved in water, made basic (pH 11) with 50% sodium hydroxide, and extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and concentrated to provide a gum. This was purified by flash column chromatography (4% methanol/dichloromethane, containing 0.4% ammonium hydroxide) to provide the product (304 mg, 61%) as a white solid. 1H NMR (300 mHz, CD3OD) δ7.13 (m, 2H), 6.96 (m, 2H), 3.36 (m, 3H), 2.87 (m, 3H), 2.78 (m, 1H), 2.56 (m, 1H), 2.49 (m, 2H), 2.40 (m, 2H), 1.95 (m, 1H), 1.8-1.6 (m, 4H), 1.50 (m, 1H), 0.95 (m, 1H), ESI MS: (M+H)+=341.2.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 5.5 h
  2. customThe solvents were removed
  3. dissolutionthe residue was dissolved in water
  4. extractionextracted with dichloromethane
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. concentrationconcentrated
  7. customto provide a gum
  8. customThis was purified by flash column chromatography (4% methanol/dichloromethane, containing 0.4% ammonium hydroxide)

Sources & evidence

ORD record
ord-3710da3b0f354278a107d51fceec9004
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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