Triphenylphosphine → N-tert-butoxycarbony-cis-4-(N3-benzoylthymin-1-yl)-L-proline diphenylmethyl ester

HRID 2186584Notes

Reaction equation

HRID 2186584 reaction equation
[C:1]1([CH:7]([O:14][C:15](=[O:29])[C@@H:16]2[CH2:20][C@@H:19](O)[CH2:18][N:17]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:49]([N:57]1[C:62](=[O:63])[C:61]([CH3:64])=[CH:60][NH:59][C:58]1=[O:65])(=[O:56])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]1([CH:7]([O:14][C:15](=[O:29])[C@@H:16]2[CH2:20][C@H:19]([N:59]3[CH:60]=[C:61]([CH3:64])[C:62](=[O:63])[N:57]([C:49](=[O:56])[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:58]3=[O:65])[CH2:18][N:17]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 10933275N3-benzoylthymineHCID 21348449N-tert-butoxycarbonyl-trans-4-hydroxy-L-proline diphenylmethyl ester

Product 1

HCID 10817506N-tert-butoxycarbony-cis-4-(N3-benzoylthymin-1-yl)-L-proline diphenylmethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

N-Boc-trans-4-hydroxy-Lroline diphenylmethyl ester (2a) (0.425 g, 1.07 mmol), triphenylphosphine (0.290 g, 1.10 mmol) and N3-benzoylthymine (0.250 g, 1.09 mmol) were dissolved in dry THF (10 ml) and the solution was cooled to −15° C. DEAD (180 μL, 1.10 mmol) was then added dropwise with stirring. The reaction mixture was stirred under argon at room temperature overnight. The solvent was evaporated and the residue was chromatographed on silica gel using dichloromethane-acetone 20:1 as eluant to give N-tert-butoxycarbony-cis-4-(N3-benzoylthymin-1-yl)-L-proline diphenylmethyl ester (3a) (Rf 0.56), which was recrystallised from ethanol to give a white fluffy solid (0.310 g, 51%), m.p. 183-185° C., (Found C, 68.9; H, 5.5; N, 6.7%; C35H35N3O7 requires C, 69.0; H, 5.8; N, 6.9%), δH (200 MHz; CDCl3) 1.30 and 1.49 (9H, 2xbr s, Boc rotamers), 1.82 (3H, br s, thymine CH3), 2.05 and 2.85 [2H, br m, CH2(3′)], 3.65 (1H, br m) and 4.02 (1H, dd, J=12.0, 8.0 Hz)[CH2(5′)], 4.54 [1H, br m, CH(2′)], 5.26 [1H, br m, CH(4′)], 6.94 (1H, s, CHPh2), 7.12 and 7.18 [1H, 2xbr s, CH(6) rotamers], 7.30-7.42 (10H, br m, phenyl CH), 7.50 (2H, t, J=7.9 Hz, benzoyl m-CH), 7.67 (1H, t, J=7.0 Hz, benzoyl p-CH), 7.92 (2H, d, J=7.0 Hz, benzoyl o-CH); δC (50.28 MHz; CDCl3) 12.3 (thymine CH3), 27.9 and 28.2 (Boc CH3 rotamers), 34.9 and 35.3 [CH2(3′) rotamers], 49.3 and 49.4 [CH2(5′) rotamers], 52.1 and 52.5 [CH(4′) rotamers], 57.5 [CH2(2′)], 78.1 and 78.4 (CHPh2 rotamers), 81.3 (Boc C), 111.7 [C(5)], 126.9-130.6 (aromatic CH), 131.6 (benzoyl C), 135.3 (benzoyl p-CH), 136.0 and 136.2 [CH(6) rotamers], 139.4 (phenyl C), 150.1 [C(2)], 153.6 (Boc CO), 162.6 [C(4)], 169.1 (benzoyl CO), 171.6 (ester CO); m/z (FAB+) 632 (M+Na+, 10%), 610 (M+H+, 39), 554 ([M−C4H8+H]+, 27), 506 ([M−PhCO+H]+, 18), 338 ([M-PhCO-Ph2CH+, 20), 266 (31), 231 (BzT+H+, 52), 167 (Ph2CH+, 100), 105 (PhCO+, 24), 57 (C4H9+, 28); νmax (KBr)/cm31 1 1751, 1694 and 1659 (C═O); [α]D≅−17.2 (c=1.0, DMF).

Workup

  1. stirringThe reaction mixture was stirred under argon at room temperature overnight
  2. customThe solvent was evaporated
  3. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-9b4524cefd234e1ca3571230f5c0ac46
Source dataset
uspto-grants-2002_06
Patent number
US06403763B1

Reaction notes

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