Potassium Carbonate → HCID 10555454, compound

HRID 51194Notes

Reaction equation

HRID 51194 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: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

7

Reactant 4

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

Product 1

HCID 10555454HCID 10555454, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

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, 2.20mmol) 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 purified 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.C2H5OH.H2O requires C, 65.6; H, 6.4; N, 8.5%), δH (200 MHz; CDCl3) 1.30 and 1.49 (9H, 2×s, Boc rotamers), 2.20 and 2.90 [2H, br m, CH2(3′)], 3.50-3.80 and 3.95-4.15 [2H, 2×br m, CH2(5′)], 4.45-4.70 [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]D23−13.6 (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. customwas purified by column chromatography (SiO2, ethyl acetate)
  6. customevaporated
  7. customto give the N1-isomer (0.299 g, 25%) as a white foam
  8. customRecrystallisation from ethanol-water

Sources & evidence

ORD record
ord-90f9079d893342209cb42de9b4b7bd1c
Source dataset
uspto-grants-2004_03
Patent number
US06713603B2

Reaction notes

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