Water → HCID 58979690, compound

HRID 1180726Notes

Reaction equation

HRID 1180726 reaction equation
[CH2:1]([C:8]1([O:12][C:13]([NH:15][C@@H:16]([CH2:21][CH2:22][CH2:23][CH3:24])[C:17]([O:19]C)=O)=[O:14])[CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+].[C:28]1([P:34](=[CH:47][C:48]#[N:49])([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.O>O1CCCC1.O.CN(C)C1C=CN=CC=1>[C:48]([C:47](=[P:34]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:17]([C@@H:16]([NH:15][C:13](=[O:14])[O:12][C:8]1([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH2:10][CH2:11]1)[CH2:21][CH2:22][CH2:23][CH3:24])=[O:19])#[N:49]

Participants

7

Reactant 4

HCID 962WaterHCID 85524(Triphenylphosphoranylidene)acetonitrileHCID 168937Lithium hydroxide, monohydrateHCID 58979704HCID 58979704, compound

Product 1

HCID 58979690HCID 58979690, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 21881883Oxolane--water (1/1)Solvent

Procedure

To 2.44 g (7.32 mmol) of methyl(2S)-2-({[(1-benzylcyclobutyl)oxy]carbonyl}amino)hexanoate in 24 mL of tetrahydrofuran:water (1:1) was added 429.9 mg (10.24 mmol) of lithium hydroxide monohydrate and the mixture was stirred at room temperature for 4 h. The solution was concentrated and extracted with diethyl ether. The aqueous layer was acidified with 1 N hydrochloric acid and extracted with diethyl ether. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was dissolver in 36 mL of dichloromethane, then 44.7 mg (365.9 μmol) of 4-dimethylaminopyridine was added. To this solution was added 2.31 g (7.68 mmol) of (triphenylphosphoranylidene)acetonitrile, followed by 1.55 g (8.05 mmol) of 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide, and the mixture was stirred at room temperature for 17 h. Water was added to the solution and it was extracted with ethyl acetate. The organic layer was washed with 10% citric acid, followed by saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography eluting with an ethyl acetate:hexanes solution (1:1) to give 3.25 g (74%) of 1-benzylcyclobutyl(1S)-1-[cyano(triphenylphosphoranylidene)acetyl]pentylcarbamate. Rf=0.25 (1:1 ethyl acetate:hexanes); 1H NMR (300 MHz, DMSO-d6) δ 7.75-7.66 (m, 3H), 7.64-7.54 (m, 12H), 7.20-7.14 (m, 5H), 7.03 (d, J=8 Hz, 1H), 4.55-4.50 (m, 1H), 3.21 (m, 2H), 2.24-2.16 (m, 2H), 2.14-2.06 (m, 2H), 1.80-1.70 (m, 2H), 1.70-1.60 (m, 1H), 1.60-1.46 (m, 1H), 1.42-1.24 (m, 4H), 0.89 (t, J=7 Hz, 3H); ES-LCMS m/z 603 (M+H).

Workup

  1. concentrationThe solution was concentrated
  2. extractionextracted with diethyl ether
  3. extractionextracted with diethyl ether
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolver in 36 mL of dichloromethane
  8. stirringthe mixture was stirred at room temperature for 17 h
  9. extractionwas extracted with ethyl acetate
  10. washThe organic layer was washed with 10% citric acid
  11. dry with materialThe organic layer was dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel column chromatography
  15. washeluting with an ethyl acetate

Sources & evidence

ORD record
ord-b8f1d3ad0fad4d6ea4b6745cef3ed35c
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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