Sodium Chloride → {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180769Notes

Reaction equation

HRID 1180769 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([CH2:12][C:13]3([CH2:17][OH:18])[CH2:16][CH2:15][CH2:14]3)[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19](Cl)(Cl)=[O:20].[NH2:23][C@@H:24]([CH2:38][CH2:39][CH2:40][CH3:41])[CH:25]([OH:37])[C:26]([NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30])=[O:27].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:37][CH:25]([C@@H:24]([NH:23][C:19](=[O:20])[O:18][CH2:17][C:13]1([CH2:12][C:9]2[S:10][CH:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=2)[CH2:16][CH2:15][CH2:14]1)[CH2:38][CH2:39][CH2:40][CH3:41])[C:26](=[O:27])[NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30]

Participants

10

Reactant 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11737047{1-[(4-Phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methanol

Product 1

HCID 11753176{1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamateYield 98.2%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.16 g (0.63 mmol) of {1-[(4-phenyl-1,3-thiazol-2-yl)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 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 7 h, 30 mL of ethyl acetate and 20 mL of saturated sodium chloride were 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 using ethyl acetate:hexane (1:1) as the eluent to afford 0.34 g (98%) of {1-[(4-phenyl-1,3-thiazol-2-yl)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 7.90, 7.92 (2s, 1H), 7.46-7.18 (m, 10 H), 5.61 (d, J=9 Hz, 1H), 5.14-5.01 (m, 2H), 4.19-4.06 (m, 4H), 3.88 (m, 1H), 3.23 (s, 2H), 2.21-1.50 (m, 10 H), 1.46 (d, J=7 Hz, 3H), 1.37-1.27 (m, 2H), 0.94 (m, 3H). LC-MS m/z 550 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 3 mL of tetrahydrofuran
  3. stirringAfter stirring for 7 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

Sources & evidence

ORD record
ord-e7fbfbd0f2d34a368692cf53ba6b0f18
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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