Pyridine → 2-(Trimethylsilyl)ethyl 2-deoxy-4-o-diphenylphosphono-3-o-[(r)-3-tetradecanoyloxytetradecanoyl]-6-o-(2,2,2-trichloro-1,1-dimethylethoxycarbonyl)-2-(2,2,2-trichlorethoxycarbonylamino)-beta-d-glucopyranoside
Reaction equation
[C:1]([O:16][C@H:17]([CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:18][C:19]([O:21][C@H:22]1[C@H:34]([OH:35])[C@@H:33]([CH2:36][OH:37])[O:32][C@@H:24]([O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C@@H:23]1[NH:38][C:39]([O:41][CH2:42][C:43]([Cl:46])([Cl:45])[Cl:44])=[O:40])=[O:20])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].N1C=CC=CC=1.Cl[C:65]([O:67][C:68]([CH3:74])([CH3:73])[C:69]([Cl:72])([Cl:71])[Cl:70])=[O:66].N1(C2C=CN=CC=2)CCCC1.C(N(CC)C(C)C)(C)C.[P:95](Cl)([O:104][C:105]1[CH:110]=[CH:109][CH:108]=[CH:107][CH:106]=1)([O:97][C:98]1[CH:103]=[CH:102][CH:101]=[CH:100][CH:99]=1)=[O:96]>C(Cl)Cl>[C:98]1([O:97][P:95]([O:35][C@@H:34]2[C@@H:33]([CH2:36][O:37][C:65]([O:67][C:68]([CH3:74])([CH3:73])[C:69]([Cl:72])([Cl:71])[Cl:70])=[O:66])[O:32][C@@H:24]([O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:31])[CH3:30])[C@H:23]([NH:38][C:39]([O:41][CH2:42][C:43]([Cl:45])([Cl:46])[Cl:44])=[O:40])[C@H:22]2[O:21][C:19](=[O:20])[CH2:18][C@H:17]([O:16][C:1](=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])([O:104][C:105]2[CH:110]=[CH:109][CH:108]=[CH:107][CH:106]=2)=[O:96])[CH:99]=[CH:100][CH:101]=[CH:102][CH:103]=1Participants
Reactant 6
HCID 1049Pyridine
HCID 755674-Pyrrolidinopyridine
HCID 75654Diphenyl chlorophosphate
HCID 81531Diisopropylethylamine
HCID 51066062,2,2-Trichloro-tert-butyl chloroformate
HCID 108658552-(trimethylsilyl)ethyl 2-deoxy-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-2-(2,2,2-trichloroethoxycarbonylamino)-beta-D-glucopyranosideProduct 1
Reagents, catalysts & solvents 1
Procedure
A solution of compound 7 (10.9 g, 12 mmol) and pyridine (2 ml, 25 mmol) in CH2Cl2 (125 ml) at 0° C. was treated dropwise over 15 min with a solution of 2,2,2-trichloro-1,1-dimethylethyl chloroformate (3.17 g, 13.2 mmol) in CH2Cl2 (25 ml). The reaction mixture was allowed to warm slowly to ambient temperature over 3.5 h. 4-Pyrrolidinopyridine (0.89 g, 6.0 mmol), N,N-diisopropylethylamine (10.5 ml 60 mmol) and diphenyl chlorophosphate (3.7 ml, 18 mmol) were added sequentially and the resulting mixture was stirred for 5 h at room temperature. The reaction mixture was diluted with CH2Cl2 (500 ml), washed with cold 7.5% aqueous HCl (2×250 ml), water (250 ml), saturated aqueous NaHCO3 (250 ml), dried (Na2SO4), and then concentrated. The residue obtained was purified by flash chromatography on silica gel eluting with 12.5% EtOAc-hexanes to give 15.1 g (95%) of 2-(trimethylsilyl)ethyl 2-deoxy-4-O-diphenylphosphono-3-O-[(R)-3-tetradecanoyloxytetradecanoyl]-6-O-(2,2,2-trichloro-1,1-dimethylethoxycarbonyl)-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranoside (compound 8) as a viscous oil: 1H NMR (CDCl3) δ0.0 (s, 9H), 0.8-1.0 (m, 8H), 1.1-1.65 (m, 42H), 1.83 and 1.90 (2s, 6H), 2.15-2.45 (m, 4H), 3.34 (q, 1H, J=˜8 Hz), 3.37 (m, 1H), 3.81 (m, 1H), 3.95 (m, 1H), 4.27 (dd, 1H, J=12, 5 Hz), 4.34 (d, 1H, J=12 Hz), 4.58 (d, 1H, J=12 Hz), 4.66 (q, 1H, J=9 Hz), 4.86 (d, 1H, J=12 Hz), 5.03 (d, 1H, J=7.9 Hz), 5.21 (m, 1H), 5.54-5.70 (m, 2H), 7.2-7.8 (m, 10H).
Workup
- washwashed with cold 7.5% aqueous HCl (2×250 ml), water (250 ml), saturated aqueous NaHCO3 (250 ml)
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- customThe residue obtained
- customwas purified by flash chromatography on silica gel eluting with 12.5% EtOAc-hexanes
Sources & evidence
- ORD record
- ord-bff431d7c6bd406b93d4665e708b06eb
- Source dataset
- uspto-grants-2002_06
- Patent number
- US06399590B2
Reaction notes
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