Sodium Chloride → (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180772

Reaction equation

HRID 1180772 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[S:7][CH2:8][C:9]1([CH2:13][OH:14])[CH2:12][CH2:11][CH2:10]1.[C:15](Cl)(Cl)=[O:16].[NH2:19][C@@H:20]([CH2:34][CH2:35][CH2:36][CH3:37])[CH:21]([OH:33])[C:22]([NH:24][C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26])=[O:23].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:33][CH:21]([C@@H:20]([NH:19][C:15](=[O:16])[O:14][CH2:13][C:9]1([CH2:8][S:7][C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[CH2:10][CH2:11][CH2:12]1)[CH2:34][CH2:35][CH2:36][CH3:37])[C:22](=[O:23])[NH:24][C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26]

Participants

10

Reactant 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11435800(1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methanol

Product 1

HCID 11397962(1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamateYield 70%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.132 g (0.625 mmol) of (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl) methanol in 2 mL of dichloromethane cooled to 0° C. was added a 1.0 M solution of 0.94 mL (1.41 mmol) of phosgene in toluene and the contents were stirred for 16 h. The reaction mixture was concentrated and the residue was dissolved in 3 mL of tetrahydrofuran, and added to a 0° C. solution of 0.165 g (0.63 mmol) of (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide and 0.325 mL (1.89 mmol) of N,N-diisopropylethylamine in 2 mL of tetrahydrofuran. After stirring for 6 h, 30 mL of ethyl acetate and 20 mL of saturated sodium chloride was added. The organic phase was isolated, dried using magnesium sulfate, and concentrated under vacuum to afford the crude product which was purified by silica gel chromatography eluting with ethyl acetate to afford 0.220 g (70%) of (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a colorless oil. 1H NMR (300 MHz, CDCl3)) δ 7.63-7.52 (m, 1H), 7.41 (m, 1H), 7.39-7.15 (m, 5H), 6.91, 6.98 (2s, 1H), 6.03 (br s, 1H), 5.69 (m, 1H), 5.19-5.11 (m, 1H), 4.18-3.95 (m, 4H), 3.61, 3.63 (2s, 2H), 3.28 (m, 2H), 2.21-1.61 (m, 10H), 1.60-1.16 (m, 5H), 0.90 (m, 3H). LC-MS m/z 503 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 3 mL of tetrahydrofuran
  3. stirringAfter stirring for 6 h
  4. customThe organic phase was isolated
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customto afford the crude product which
  8. customwas purified by silica gel chromatography
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-3feacce7c9fb4b0e939f4645d1eb37c2
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Linked notes

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