Diisopropylethylamine → 5'-O-(4,4'-di-3,5-hexadienoxytrityl)thymidine 3'-phosphoramidite

HRID 363547Notes

Reaction equation

[CH2:1]([O:7][C:8]1[CH:50]=[CH:49][C:11]([C:12]([O:32][CH2:33][C@H:34]2[O:38][C@@H:37]([N:39]3[CH:47]=[C:45]([CH3:46])[C:43](=[O:44])[NH:42][C:40]3=[O:41])[CH2:36][C@@H:35]2[OH:48])([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH:22]=[CH:23][CH:24]=[CH2:25])=[CH:15][CH:14]=2)=[CH:10][CH:9]=1)[CH2:2][CH:3]=[CH:4][CH:5]=[CH2:6].C(N(C(C)C)CC)(C)C.C(CC[O:64][P:65](Cl)[N:66](C(C)C)C(C)C)#N>ClCCl>[P:65]([O:48][C@@H:35]1[C@@H:34]([CH2:33][O:32][C:12]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:11]2[CH:49]=[CH:50][C:8]([O:7][CH2:1][CH2:2][CH:3]=[CH:4][CH:5]=[CH2:6])=[CH:9][CH:10]=2)[C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][CH:22]=[CH:23][CH:24]=[CH2:25])=[CH:17][CH:18]=2)[O:38][C@@H:37]([N:39]2[CH:47]=[C:45]([CH3:46])[C:43](=[O:44])[NH:42][C:40]2=[O:41])[CH2:36]1)([NH2:66])[OH:64]

Participants

Conditions

Temperature: 0 °C

Procedure

Compound 31 (3.0 grams, 4.43 mmol) was dissolved in anhydrous dichloromethane and diisopropylethylamine (2.7 mL; 15.5 mmol) was added. The solution was cooled to 0° C. and 2-cyanoethyl-N,N-diisopropylchlorophosphoramidite (2.0 mL, 8.86 mmol) was added. The reaction mixture was allowed to warm to room temperature with stirring under argon. After 4 hours the solution was diluted with dichloromethane and washed with a 5% aqueous solution of sodium bicarbonate (2×). The organic phase was dried (MgSO4), concentrated in vacuo, and purified by column chromatography (silica gel; EtOAc/hexane, 3/7) to afford 2.8 grams (72%) of compound 32 as a fluffy white solid. 1H NMR (300 MHz, CDCl3) δ1.01-1.20 (m, 12H), 1.41 (s, 3H), 2.25-2.67 (m, 8H), 3.26-4.22 (m, 11H), 4.60-4.65 (m, 1H), 5.02 (dd, J=1.5, 10.4 Hz, 2H), 5.14 (dd, J=1.5, 17.3 Hz, 2H), 5.69-5.84 (m, 2H), 6.11-6.48 (m, 5H), 6.82 (dd, J=3.2, 8.9 Hz, 4H), 7.16-7.43 (m, 9H), 7.62 (d, J=15.2 Hz, 1H), 8.05 (bs, 1H); 31P NMR (300 MHz, DMSO-d6) 152.9, 152.4; Anal. Calcd for C50H61N4O8P1 (877.0276): C, 68.48; H, 7.01; N, 6.39. Found: C, 68.48; H, 7.22; N, 6.33. ##STR18##

Workup

temperatureto warm to room temperature
washwashed with a 5% aqueous solution of sodium bicarbonate (2×)
dry with materialThe organic phase was dried (MgSO4)
concentrationconcentrated in vacuo
custompurified by column chromatography (silica gel; EtOAc/hexane, 3/7)

Sources & evidence

ORD record: ord-6bdc26aa7ff641478c80471ff582afed
Source dataset: uspto-grants-1999_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05874532

Reaction notes

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