Methanesulfonyl chloride → HCID 86707927, compound

HRID 595375Notes

Reaction equation

HRID 595375 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH2:6]([N:8]([C:16]1[S:17][C@H:18]2[O:24][C@H:23]([CH2:25][OH:26])[C@@H:22]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[C@H:21]([O:37][CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[C@H:19]2[N:20]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH3:7]>N1C=CC=CC=1.C(Cl)Cl>[CH3:1][S:2]([O:26][CH2:25][C@H:23]1[O:24][C@H:18]2[C@H:19]([N:20]=[C:16]([N:8]([C:9]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:15])[CH2:6][CH3:7])[S:17]2)[C@@H:21]([O:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=2)[C@@H:22]1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)(=[O:4])=[O:3]

Participants

5

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 67982258HCID 67982258, compound

Product 1

HCID 86707927HCID 86707927, compoundYield 99.8%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (0.038 mL, 0.495 mmol) was added in portions to a stirred solution of tert-butyl ethyl(-(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)carbamate (0.190 g, 0.323 mmol) in dry pyridine (5 mL) at −20° C. After 3 h, the reaction mixture was diluted with DCM (20 mL) and the DCM extract was washed with satd. NaHCO3, brine, dried over Na2SO4 and concentrated. Residual pyridine was removed by co-evaporation with hexanes. The crude product was purified by silica gel column chromatography (3:7 EtOAc/hexanes) to give (-(3aR,5R,6S,7R,7aR)-2-((tert-butoxycarbonyl)(ethyl)amino)-6,7-bis((4-methoxybenzyl)oxy)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)methyl methanesulfonate (0.215 g, 99.6%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J=8.5 Hz, 2H), 7.17 (d, J=8.5 Hz, 2H), 6.91-6.83 (m, 4H), 6.01 (d, J=6.88 Hz, 1H), 4.66 (d, J=11.6 Hz, 1H), 4.60 (d, J=11.6 Hz, 1H), 4.52 (d, J=11.1 Hz, 1H), 4.42-4.36 (m, 2H), 4.27-4.23 (m, 3H), 3.96-3.84 (m, 2H), 3.8 (s, 3H), 3.79 (s, 3H), 3.55 (m, 2H), 2.98 (s, 3H), 1.52 (s, 9H), 1.20 (t, J=6.9 Hz, 3H).

Workup

  1. extractionthe DCM extract
  2. washwas washed with satd
  3. dry with materialNaHCO3, brine, dried over Na2SO4
  4. concentrationconcentrated
  5. customResidual pyridine was removed by co-evaporation with hexanes
  6. customThe crude product was purified by silica gel column chromatography (3:7 EtOAc/hexanes)

Sources & evidence

ORD record
ord-30f9b94468f046f7952e5f748123d01d
Source dataset
uspto-grants-2016_01
Patent number
US09243020B2

Reaction notes

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