Hydrochloric Acid → Carbamic acid, N-[(1S)-1-(4-chloro-2-pyridinyl)-3-buten-1-yl]-, 1,1-dimethylethyl ester

HRID 1481268Notes

Reaction equation

HRID 1481268 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@@H:8]([NH:12][S@](C(C)(C)C)=O)[CH2:9][CH:10]=[CH2:11])[CH:3]=1.Cl.CCN(CC)CC.[O:27](C(OC(C)(C)C)=O)[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=O>CO.ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@@H:8]([NH:12][C:28](=[O:27])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:9][CH:10]=[CH2:11])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 66744179(S)-N-((S)-1-(4-Chloropyridin-2-yl)but-3-enyl)-2-methylpropane-2-sulfinamide

Product 1

HCID 66744734Carbamic acid, N-[(1S)-1-(4-chloro-2-pyridinyl)-3-buten-1-yl]-, 1,1-dimethylethyl esterYield 93.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

1B (75 g, 261 mmol) was dissolved in methanol (1500 mL). Hydrochloric acid (6N) (750 ml, 4.5 mol) was added. The reaction was stirred at rt for 2-3 hrs and then was concentrated. The residue was diluted with water (2 L), washed with ethyl acetate (500 ml). The aqueous layer was basified with saturated sodium carbonate solution, extracted into ethyl acetate (3×1 L). The combined organic layers were washed with water (1×1 L) and brine (1×1 L), dried over sodium sulfate, filtered and conc. under vacuum at 50-55° C. to give crude product (43 g, 90%). MS (ESI) m/z: 183.2 (M+H)+. The crude product (42 g, 230 mmol) was dissolved in dichloromethane (420 mL), Et3N (32.1 mL, 230 mmol) was added followed by dropwise addition of BOC2O (53.4 mL, 230 mmol). The reaction was stirred at rt for 2-3 hrs. The reaction was diluted with excess DCM (1 L), washed with water (1×500 ml) and brine (1×500 ml). The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was then purified using silica gel chromatography to give 1C (61 g, 86%) as a pale yellow solid. MS (ESI) m/z: 283.2 (M+H)+.

Workup

  1. concentrationwas concentrated
  2. additionThe residue was diluted with water (2 L)
  3. washwashed with ethyl acetate (500 ml)
  4. extractionextracted into ethyl acetate (3×1 L)
  5. washThe combined organic layers were washed with water (1×1 L) and brine (1×1 L)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered and conc. under vacuum at 50-55° C.
  8. customto give crude product (43 g, 90%)
  9. stirringThe reaction was stirred at rt for 2-3 hrs
  10. washwashed with water (1×500 ml) and brine (1×500 ml)
  11. dry with materialThe organic layer was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was then purified

Sources & evidence

ORD record
ord-918691375aef49c48823618438438876
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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