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

HRID 1438127Notes

Reaction equation

HRID 1438127 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

5

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 6586Methyl chloroformateHCID 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).

Workup

  1. extractionThe product was extracted with ethyl acetate
  2. washwas washed with brine
  3. dry with materialdried over sodium sulfate
  4. customAfter evaporation of the solvent
  5. dissolutionthe crude product was redissolved in ethyl acetate (1.5 mL)
  6. additionhydrogen chloride (2 mL, 4M in dioxane) was added
  7. stirringThe reaction was stirred for 3 h at rt
  8. customThe solvent was removed

Sources & evidence

ORD record
ord-c8db521ee1b24bef8317b3f4834364e6
Source dataset
uspto-grants-2009_11
Patent number
US07622585B2

Reaction notes

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