HCID 178447109, compound → HCID 178447110, compound

HRID 340811Notes

Reaction equation

HRID 340811 reaction equation
C(OC(/[N:8]=[C:9](\[NH:32]C(OC(C)(C)C)=O)/[NH:10][C@H:11]1[CH2:16][C:15]([C:17]([OH:19])=[O:18])=[CH:14][C@@H:13]([O:20][CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C@@H:12]1[NH:26][C:27](=[O:31])[CH:28]([F:30])[F:29])=O)(C)(C)C>FC(F)(F)C(O)=O.C(Cl)Cl>[F:29][CH:28]([F:30])[C:27]([NH:26][C@@H:12]1[C@@H:11]([NH:10][C:9]([NH2:32])=[NH:8])[CH2:16][C:15]([C:17]([OH:19])=[O:18])=[CH:14][C@H:13]1[O:20][CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])=[O:31]

Participants

4

Reactant 1

HCID 178447109HCID 178447109, compound

Product 1

HCID 178447110HCID 178447110, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of (3R,4R,5S)-ethyl 5-((Z)-2,3-bis(tert-butoxycarbonyl)guanidino-4-(2,2-difluoroacetamido)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 6b (250 mg) in dioxane (5 ml) 5% solution of lithium hydroxide (2.5 ml) was added and the reaction mixture was stirred at room temperature for 45 min. Then lithium hydroxide was passivated by adding acetic acid (300 mcl), the solvents were evaporated in vacuo. The solid was extracted with isopropyl alcohol, the extract was dried over Na2SO4 and evaporated in vacuo. It gives (3R,4R,5S)-5-((Z)-2,3-bis(tert-butoxycarbonyl)guanidino)-4-(2,2-difluoroacetamido)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylic acid 8b (200 mg, 84%). LCMS (M+H): found 563; calculated 562.62. The obtained acid 8b (200 mg) was dissolved in 10% solution of trifluoroacetic acid in methylene chloride (2 ml) and stirred at room temperature for 12 h. Then the solvents were evaporated in vacuo. (3R,4R,5S)-4-(2,2-Difluoroacetamido)-5-guanidino-3-(pentan-3-yloxy)cyclohex-1-enecarboxylic acid 1.4 was separated by HPLC method. LCMS (M+H): found 363; calculated 362.28. 1H NMR (DMSO-d6), 400 MHz: 8.68 (d, J=8.4 Hz, 1H), 7.6 (d, J=10 Hz, 1H), 7.26 (br, 2H), 6.91 (br, 2H), 6.63 (s, 1H), 6.27 (t, J=53.6 Hz, 1H), 4.18 (d, J=8 Hz, 2H), 4.09 (m, 1H), 3.54 (q, J=10 Hz, 1H), 3.39 (m, 2H), 2.57 (dd, J1=18 Hz, J2=6 Hz, 1H), 2.31 (m, 1H), 1.44 (m, 4H), 0.85 (t, J=8 Hz, 3H), 0.795(t, J=7.6 Hz, 3H).

Workup

  1. customThen the solvents were evaporated in vacuo
  2. custom(3R,4R,5S)-4-(2,2-Difluoroacetamido)-5-guanidino-3-(pentan-3-yloxy)cyclohex-1-enecarboxylic acid 1.4 was separated by HPLC method

Sources & evidence

ORD record
ord-2888fec37a00491d9deb4c19598c1250
Source dataset
uspto-grants-2014_11
Patent number
US08895613B2

Reaction notes

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