1,1'-Carbonyldiimidazole → Carbamic acid, N-[(1R,2S)-1-[[(cyclopropylsulfonyl)amino]carbonyl]-2-ethenylcyclopropyl]-, 1,1-dimethylethyl ester

HRID 734250Notes

Reaction equation

HRID 734250 reaction equation
[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([OH:16])=O)[CH2:11][C@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:29]1([S:32]([NH2:35])(=[O:34])=[O:33])[CH2:31][CH2:30]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([NH:35][S:32]([CH:29]2[CH2:31][CH2:30]2)(=[O:34])=[O:33])=[O:16])[CH2:11][C@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10376443(1R,2S)-1-(((1,1-Dimethylethoxy)carbonyl)amino)-2-ethenylcyclopropanecarboxylic acidHCID 15765418Cyclopropanesulfonamide

Product 1

HCID 45480526Carbamic acid, N-[(1R,2S)-1-[[(cyclopropylsulfonyl)amino]carbonyl]-2-ethenylcyclopropyl]-, 1,1-dimethylethyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the product of Step 1 (2.62 g, 11.5 mmol) and CDI (2.43 g, 15.0 mmol) in THF (40 mL) was heated at reflux for 50 minutes under nitrogen. The solution was cooled to room temperature and transferred by cannula to a solution of cyclopropylsulfonamide (1.82 g, 15.0 mmol) in THF (10 mL). To the resulting solution was added DBU (2.40 mL, 16.1 mmol) and stirring was continued for 20 hours. The mixture was quenched with 1N HCl to pH 1 and THF was concentrated in vacuo. The suspension was extracted with ethyl acetate (2×50 mL) and the combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification by recrystallization from hexanes-ethyl acetate (1:1) afforded the title compound (2.4 g) as a white solid. The mother liquor was purified by a Biotage 40S column (eluted 9% acetone in dichloromethane) to give a second batch of the title compound (1.1 g). Both batches were combined (total yield 92%). 1H NMR (DMSO-d6) δ 0.96-1.10 (m, 4H), 1.22 (dd, J=5.5, 9.5 Hz, 1H), 1.39 (s, 9H), 1.70 (t, J=5.5 Hz, 1H), 2.19-2.24 (m, 1H), 2.90 (m, 1H), 5.08 (d, J=10 Hz, 1H), 5.23 (d, J=17 Hz, 1H), 5.45 (m, 1H), 6.85, 7.22 (s, NH (rotamers); MS m/z 331 (M++H).

Workup

  1. temperatureat reflux for 50 minutes under nitrogen
  2. customThe mixture was quenched with 1N HCl to pH 1 and THF
  3. concentrationwas concentrated in vacuo
  4. extractionThe suspension was extracted with ethyl acetate (2×50 mL)
  5. dry with materialthe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification
  9. customby recrystallization from hexanes-ethyl acetate (1:1)

Sources & evidence

ORD record
ord-e2e15c0ca69e4addb472e9cd962972dc
Source dataset
uspto-grants-2009_09
Patent number
US07592336B2

Reaction notes

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