Carbon Dioxide → HCID 59716450, compound

HRID 2224097Notes

Reaction equation

HRID 2224097 reaction equation
[C:1]([Li])([CH3:4])([CH3:3])[CH3:2].[CH3:6][CH2:7][CH2:8]CC.[S:11]1[CH:15]=[CH:14][CH:13]=[C:12]1[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20].[C:24](=[O:26])=O.C([NH2:34])C1C=CC=CC=1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>C1COCC1.CN(C=O)C>[CH2:2]([NH:34][C:24]([C:13]1[CH:14]=[CH:15][S:11][C:12]=1[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:26])[C:1]1[CH:4]=[CH:8][CH:7]=[CH:6][CH:3]=1

Participants

11

Reactant 8

HCID 280Carbon DioxideHCID 7504BenzylamineHCID 8003PentaneHCID 8471TriethylamineHCID 181649HOAtHCID 319413tert-Butyl thiophen-2-ylcarbamateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178418306HCID 178418306, compound

Product 1

HCID 59716450HCID 59716450, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyllithium in pentane (1.7 M, 42.5 mL, 72.3 mmol, 2.40 equiv) was added to a solution of tert-butyl thien-2-ylcarbamate (2-1, 6.00 g, 30.1 mmol, 1 equiv) in THF (300 mL) at −78° C. The reaction mixture was stirred for 45 min, then solid CO2 (approximately 20 g) was added and the resulting mixture was warmed to 0° C. and stirred for 30 minutes. The reaction mixture was partitioned between aqueous 1 N hydrochloric acid solution and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexanes initially, grading to 100% ethyl acetate), and the polar fractions were concentrated. A solution of the residue, benzylamine (6.61 g, 61.7 mmol, 2.05 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.91 g, 30.8 mmol, 1.02 equiv), 1-hydroxy-7-azabenzotriazole (4.19 g, 30.8 mmol, 1.02 equiv), and triethylamine (8.59 mL, 61.7 mmol, 2.05 equiv) in DMF (100 mL) was stirred at 55° C. for 24 h. The reaction mixture was concentrated, and the residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (3×100 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column (hexanes initially, grading to 100% ethyl acetate) to give tert-butyl 3-[(benzylamino)carbonyl]thien-2-ylcarbamate (2-2) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.37 (m, 5H), 6.87 (d, 1H, J=5.8 Hz), 6.69 (d, 1H, J=5.8 Hz), 6.13 (s, 1H), 4.61 (d, 2H, J=5.5 Hz), 1.52 (s, 9H).

Workup

  1. stirringstirred for 30 minutes
  2. customThe reaction mixture was partitioned between aqueous 1 N hydrochloric acid solution and ethyl acetate (2×150 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (hexanes initially
  6. concentrationwere concentrated
  7. concentrationThe reaction mixture was concentrated
  8. customthe residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (3×100 mL)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by flash column (hexanes initially

Sources & evidence

ORD record
ord-99736021dcae43f8a7b2371465d0b59b
Source dataset
uspto-grants-2008_05
Patent number
US07378411B2

Reaction notes

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