Hydrochloric Acid → (R)-Methyl(4-(isopropylsulfonyl)-3-(pyrrolidin-2-yl)phenyl)carbamate hydrochloride

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([S:20]([CH:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])=[C:6]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2C(OC(C)(C)C)=O)[CH:7]=1.[Cl:26][C:27]([O:29]C)=[O:28].Cl.N1C=CC=C[CH:33]=1>>[ClH:26].[CH3:33][N:1]([C:2]1[CH:3]=[CH:4][C:5]([S:20]([CH:23]([CH3:24])[CH3:25])(=[O:21])=[O:22])=[C:6]([C@H:8]2[CH2:12][CH2:11][CH2:10][NH:9]2)[CH:7]=1)[C:27](=[O:28])[OH:29]

Participants

Reactant 4

HCID 313Hydrochloric Acid

HCID 1049Pyridine

HCID 6586Methyl chloroformate

HCID 57942759(R)-tert-butyl 2-(5-amino-2-(isopropylsulfonyl)phenyl)pyrrolidine-1-carboxylate

Product 1

HCID 67440170(R)-Methyl(4-(isopropylsulfonyl)-3-(pyrrolidin-2-yl)phenyl)carbamate hydrochloride

Procedure

To 40A (0.1 g, 0.27 mmol) in pyridine (1 mL) at 0° C. was added methyl chloroformate (57 μL, 0.54 mmoL). After 2.0 h of stirring at rt the reaction was acidified with 1M HCl to pH 3-4. The product was extracted with ethyl acetate and was washed with brine and dried over sodium sulfate. After evaporation of the solvent, the crude product was redissolved in ethyl acetate (1.5 mL) and hydrogen chloride (2 mL, 4M in dioxane) was added. The reaction was stirred for 3 h at rt. The solvent was removed and placed on the lyophilizer to give 0.15 g white solid 44A. 1H NMR (400 MHz, Methanol-d4) δ ppm 1.25 (t, J=7.09 Hz, 3H) 1.37 (d, J=6.85 Hz, 3H) 2.13-2.31 (m, 1H) 2.31-2.47 (m, 2H) 2.47-2.63 (m, 1H) 3.36-3.56 (m, 3H) 3.73-3.91 (m, 3H) 5.43 (t, J=7.70 Hz, 1H) 7.66 (dd, J=8.80, 2.20 Hz, 1H) 7.97 (d, J=8.80 Hz, 1H) 8.11 (d, J=1.96 Hz, 1H).