Benzyl mercaptan → HCID 67081887, compound

HRID 1921078Notes

Reaction equation

HRID 1921078 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([CH2:13]OS(C)(=O)=O)[C@@H:10]([OH:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:20]([SH:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[H-].[Na+]>CN(C=O)C.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([CH2:13][S:27][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@@H:10]([OH:19])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 7509Benzyl mercaptanHCID 24758Sodium hydrideHCID 86606462HCID 86606462, compound

Product 1

HCID 67081887HCID 67081887, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×

Procedure

(3R,4R)-1-tert-Butoxycarbonyl-3-hydroxy-4-(mesyloxymethyl)pyrrolidine (see Example 34, 1.10 g, 3.7 mmol) was dissolved in DMF (2 mL) and added dropwise to a solution of benzyl mercaptan (870 μL, 7.4 mmol) and NaH (270 mg, 60% oil dispersion, 6.8 mmol) In DMF (10 mL) and stirred at room temp. for 1 h. The reaction was diluted with toluene, washed with water then brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography to afford (3R,4S)-1-tert-butoxycarbonyl-3-hydroxy-4-(benzylthiomethyl)pyrrolidine as a syrup. Without further characterisation, the product was dissolved in MeOH (5.0 mL) and cHCl (1.0 mL) and concentrated in vacuo to afford (3R,4S)-3-hydroxy-4-(benzylthiomethyl)pyrrolidine hydrochloride (53) as a syrup (730 mg, 76% overall yield for two steps). 1H NMR (D2O) δ 7.40-7.27 (m, 5H), 4.26-4.22 (m, 1H), 3.74 (s, 2H), 3.56 (dd, J=12.4, 7.2 Hz, 1H), 3.37 (dd, J=12.8, 5.2 Hz, 1H), 3.21 (dd, J=12.8, 3.0 Hz, 1H), 3.07 (dd, J=12.4, 5.5 Hz, 1H), 2.61-2.52 (m, 1H), 2.47-2.34 (m, 2H). 13C NMR (D2O) δ 138.7, 129.5, 129.3, 127.9, 73.5, 51.5, 48.5, 45.4, 35.9, 31.8. (MH+) calc for C12H18NOS: 224.1109. Found 224.1102.

Workup

  1. washwashed with water
  2. dry with materialbrine, dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-e3377559e7914a76aecc00078f617a0f
Source dataset
uspto-grants-2012_05
Patent number
US08173662B2

Reaction notes

Loading…