Potassium Carbonate → N-tert-Butoxycarbonyl-cis-4-(N4-benzoylcytosin-1-yl)-D-proline Diphenylmethyl Ester

HRID 2186585Notes

Reaction equation

HRID 2186585 reaction equation
[C:1]1([CH:7]([O:14][C:15](=[O:39])[C@H:16]2[CH2:20][C@H:19](OS(C3C=CC(C)=CC=3)(=O)=O)[CH2:18][N:17]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:40]([NH:48][C:49]1[CH:54]=[CH:53][NH:52][C:51](=[O:55])[N:50]=1)(=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C([O-])([O-])=O.[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C=O)C.ClCCl.C(OCC)(=O)C>[C:8]1([CH:7]([O:14][C:15](=[O:39])[C@H:16]2[CH2:20][C@@H:19]([N:52]3[CH:53]=[CH:54][C:49]([NH:48][C:40](=[O:47])[C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[N:50][C:51]3=[O:55])[CH2:18][N:17]2[C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 10530720N-boc-trans-4-tosyloxy-d-proline diphenylmethyl EsterHCID 178522337HCID 178522337, compound

Product 1

HCID 10555454N-tert-Butoxycarbonyl-cis-4-(N4-benzoylcytosin-1-yl)-D-proline Diphenylmethyl Ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A reaction mixture containing the trans-D tosylate (7) (1.10 g, 2.00 mmol), N4-benzoylcytosine (0.475 g, 2.20 mmol), anhydrous K2CO3 (0.300 g, 2.20 mmol) and 18-crown-6 (200 mg) in DMF (10 ml) was stirred at 70-80° C. under argon overnight. The white suspension was diluted with dichloromethane (75 ml), filtered through celite and the organic phase washed with water. Evaporation gave the crude product as an oil which was purfied by column chromatography (SiO2, ethyl acetate). The more polar fractions (Rf 0.33) were combined and evaporated to give the N1-isomer (0.299 g, 25%) as a white foam. Recrystallisation from ethanol-water gave white crystals of N-tert-butoxycarbonyl-cis-4-(N4-benzoylcytosin-1-yl)-D-proline diphenylmethyl ester (11), m.p. 133-135° C., (Found C, 65.8; H, 6.5; N, 8.8%; C34H34N4O6. C2HR5OH.H2O requires C, 65.6; H, 6.4; N, 8.5%), δH (200 MHz; CDCl3) 1.30 and 149 (9H, 2xs, Boc rotamers), 2.20 and 2.90 [2H, br m, CH2(3′)], 3.50-3.80 and 3.95-4.15 [2H, 2xbr m, CH2(5′)], 445-4.70 [1H, br m, CH(2′)], 5.28 [1H, br m, CH(4′)], 6.87 (1H, s, CHPh2), 7.15-7.40 (10H, m, phenyl CH), 7.40-7.75 [5H, m, CH(5), CH(6) and benzoyl m- and p-CH], 7.89 (2H, d, J=7.4 Hz, benzoyl o-CH), 8.83 (1H, br s, NH); δC (50.28 MHz; CDCl3) 27.7 and 28.0 (Boc CH3 rotamers), 34.4 and 36.0 [CH2(3′) rotamers], 49.6 and 50.5 [CH2(5′) rotamers], 54.3 and 54.9 [CH(4′) rotamers], 57.6 CH(2′)], 78.0 and 78.3 (CHPh2 rotamers), 81.3 (Boc C), 96.8 [CH(5)], 127.0-129.2 (aromatic CH), 133.4 (benzoyl C), 139.5 (aromatic C), 145.2 and 145.7 [CH(6) rotamers)], 153.8 (Boc CO rotamers), 155.6 [C(2)], 162.0 [C(4)], 166.8 (benzoyl CO), 171.3 (ester CO); m/z (ES MS) 595 (M+H+, 100%); νmax (KBr)/cm−1 1743 (C═O), 1704s (C═O); λmax (CHCl3)/nm 266 (ε/dm3.mol−1.cm−1 8.9×104), 312 (3.4×104); [α]D25 −13.6 (c=0.50, CHCl3).

Workup

  1. filtrationfiltered through celite
  2. washthe organic phase washed with water
  3. customEvaporation
  4. customgave the crude product as an oil which
  5. customevaporated
  6. customto give the N1-isomer (0.299 g, 25%) as a white foam
  7. customRecrystallisation from ethanol-water

Sources & evidence

ORD record
ord-1ba82b2b79744fa0b09f3f82adc98f77
Source dataset
uspto-grants-2002_06
Patent number
US06403763B1

Reaction notes

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