Dimethyl Sulfoxide → HCID 86701123, compound

HRID 1396295Notes

Reaction equation

HRID 1396295 reaction equation
CS(C)=O.C(Cl)(C(Cl)=O)=O.[CH2:11]([O:18][C@@H:19]1[C@@H:27]([CH2:28][OH:29])[O:26][C@H:25]2[C@H:21]([N:22]=[C:23]([N:30]([CH2:38][CH:39]=[CH2:40])[C:31](=O)OC(C)(C)C)[S:24]2)[C@H:20]1[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[CH2:11]([O:18][C@@H:19]1[C@@H:27]([CH:28]=[O:29])[O:26][C@H:25]2[C@H:21]([N:22]=[C:23]([N:30]([CH3:31])[CH2:38][CH:39]=[CH2:40])[S:24]2)[C@H:20]1[O:41][CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 69093734HCID 69093734, compound

Product 1

HCID 86701123HCID 86701123, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-30 °C

Procedure

A solution of DMSO (9.2 g, 118 mmol) in dry dichloromethane (70 mL) was treated with (COCl)2 (11.6 g, 92 mmol) at −78° C. for 30 minutes, followed by addition of tert-butyl N-[(3aR,5R,6S,7R,7aR)-6,7-bis(benzyloxy)-5-(hydroxymethyl)-3aH,5H,6H,7H,7aH-pyrano[3,2-d][1,3]thiazol-2-yl]-N-(prop-2-en-1-yl)carbamate (8 g, 15 mmol) in dichloromethane (15 mL) slowly. The resulting solution was stirred for 3 hours at −30° C., then cooled down to −78° C. again before addition of triethylamine (20 g, 180 mmol). After additional 30 minutes at −50° C., the resulting mixture was quenched by water (50 mL), and the aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic layer was dried over sodium sulfate, and concentrated to afford crude 140 as a light yellow syrup, which was dissolved into anhydrous THF (100 mL). The solution was treated with bromo(methyl)magnesium (20 ml, 40 mmol, 2M in THF) at 0° C. overnight. The reaction was then quenched with saturated aqueous NH4Cl solution (100 mL), and extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with brine (2×50 mL), dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was purified by flash column chromatography with 10%-20% ethyl acetate in petroleum ether to afford 143 as a yellow syrup (7 g, 87%, two isomers, the ratio is 1:3.8 determined by 1HNMR). (ES, m/z): [M+H]+ 555.0; 1H NMR (300 MHz, CDCl3): 7.38-7.25 (m, 10H), 6.13-6.11 (m, 1H), 5.82-5.70 (m, 1H), 5.99-4.96 (m, 2H), 4.76-4.56 (m, 2H), 4.54-4.27 (m, 6H), 4.13-3.73 (m, 3H), 1.50 (s, 9H), 1.28-1.20 (m, 3H).

Workup

  1. waitAfter additional 30 minutes at −50° C.
  2. customthe resulting mixture was quenched by water (50 mL)
  3. extractionthe aqueous layer was extracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-87f84d43fc6a4cd0adf755d8a655b3c9
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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