4-Toluenesulfonyl chloride → (R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

HRID 1909809Notes

Reaction equation

[C:1]([N:8]1[CH2:14][CH2:13][CH2:12][C@@H:9]1[CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[S:15](Cl)([C:18]1[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=1)(=[O:17])=[O:16]>N1C=CC=CC=1>[C:4]([O:3][C:1]([N:8]1[CH2:14][CH2:13][CH2:12][C@@H:9]1[CH2:10][O:11][S:15]([C:18]1[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=1)(=[O:17])=[O:16])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (R)-Boc-prolinol (500 mg, 2.48 mmol) in pyridine (1.5 mL) was added tosyl chloride (565 mg, 2.96 mmol) in pyridine (1 mL) at 0° C., and the resulting mixture was stirred at 0° C. for 20 min. before allowing it to warm to rt. The mixture was stirred for 8 h at that temperature. The solvent was removed from the resulting suspension, and aq. 1N HCl was added to the crude product and extracted with EtOAc. Organic layer was washed with saturated aq. NaHCO3 followed by water and brine. Organic layer was dried over anhy. Na2SO4 and the solvent was removed in vacuo to obtain the title product (800 mg, 91%) as a thick oil: MS; m/z 378 (M+Na); 1H NMR (400 MHz, CDCl3); δ 1.38 (m, 9H), 1.79 (m, 2H), 1.93 (m, 2H), 2.44 (s, 3H), 3.26-3.32 (m, 3H), 3.88-3.97 (m, 2H), 4.07-4.14 (m, 2H), 7.34 (br s, 2H), 7.77 (d, 2H, J=8.0 Hz); HPLC (ELSD); 99%.

Workup

temperatureto warm to rt
stirringThe mixture was stirred for 8 h at that temperature
customThe solvent was removed from the resulting suspension, and aq. 1N HCl
additionwas added to the crude product
extractionextracted with EtOAc
washOrganic layer was washed with saturated aq. NaHCO3
customOrganic layer was dried over anhy
customNa2SO4 and the solvent was removed in vacuo

Sources & evidence

ORD record: ord-62d7423221d8463e9c8e33daa03b66b6
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598359B2

Reaction notes

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