Hydrochloric Acid → HCID 58979664, compound

HRID 1180755Notes

Reaction equation

HRID 1180755 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]2([CH2:11][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])[CH2:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.O.[OH-].[Li+].Cl.[C:31]1([P:37](=[CH:50][C:51]#[N:52])([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl.CN(C)CCCN=C=NCC>O1CCCC1.O.ClCCl>[C:51]([C:50](=[P:37]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:17]([C@@H:16]([NH:15][C:13](=[O:14])[O:12][CH2:11][C:7]1([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:26][CH:25]=2)[CH2:10][CH2:9][CH2:8]1)[CH2:21][CH2:22][CH2:23][CH3:24])=[O:19])#[N:52]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 85524(Triphenylphosphoranylidene)acetonitrileHCID 168937Lithium hydroxide, monohydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58979675HCID 58979675, compound

Product 1

HCID 58979664HCID 58979664, compoundYield 300%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 760 mg (2.1 mmol) of methyl(2S)-2-[({[1-(4-fluorobenzyl)cyclobutyl]methoxy}carbonyl)amino]hexanoate in 5 mL of tetrahydrofuran was added a solution of 105 mg (2.5 mmol) of lithium hydroxide monohydrate in 5 mL of water. The reaction was heated briefly to promote homogeneity and then let stir at room temperature for 18 h. The reaction was diluted with water, acidified with iced 1M hydrochloric acid, extracted with ethyl acetate, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting carboxylic acid was dissolved in 50 mL of dichloromethane before 630 mg (2.1 mmol) of (triphenylphosphoranylidene) acetonitrile was added. The mixture was cooled to 0° C. before a catalytic amount of N,N-dimethylaminopyridine was added followed by 400 mg (2.1 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The reaction was allowed to warm to room temperature and stirred for 18 h. The mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 1:9 ethyl acetate:dichloromethane to afford 400 mg (300%) of [1-(4-fluorobenzyl)cyclobutyl]methyl(1S)-1-[cyano(triphenylphosphoranylidene)acetyl]pentylcarbamate. 1H NMR (300 MHz, DMSO-d6) δ 7.75 (m, 3H), 7.50-7.68 (m, 12H), 7.22 (m, 3H), 7.01 (t, J=9 Hz, 2H), 4.56 (m, 1H), 3.81 (dd, J=11 Hz, J=39 Hz, 2H), 2.77 (s, 2H), 1.70-1.95 (m, 7H), 1.61 (m, 1H), 1.38 (m, 4H), 0.92 (t, J=7 Hz, 3H). ES-LCMS m/z 635 (M+H).

Workup

  1. temperatureThe reaction was heated briefly
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionwas added
  6. additionwas added
  7. temperatureto warm to room temperature
  8. stirringstirred for 18 h
  9. concentrationThe mixture was concentrated under reduced pressure
  10. customthe residue was purified by silica gel chromatography
  11. washeluting with 1:9 ethyl acetate

Sources & evidence

ORD record
ord-40aa28ab8b6c4c1788b22490dbd4b3e3
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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