Benzyl chloroformate → HCID 86658527, compound

HRID 1043401Notes

Reaction equation

HRID 1043401 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:61]2[CH:66]=[CH:65][C:64]([O:67][CH3:68])=[CH:63][CH:62]=2)([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[O:10][CH2:11][C@@H:12]2[C@@H:16]([OH:17])[C@:15]([F:19])([CH3:18])[C@H:14]([N:20]3[CH:28]=[N:27][C:26]4[C:21]3=[N:22][C:23]([NH:31][C:32]([C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)([C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[N:24][C:25]=4[O:29][CH3:30])[O:13]2)=[CH:5][CH:4]=1.[CH:69]1[CH:74]=[CH:73][C:72]([CH2:75][O:76][C:77](Cl)=[O:78])=[CH:71][CH:70]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:77](=[O:78])([O:17][C@H:16]1[C@:15]([F:19])([CH3:18])[C@H:14]([N:20]2[CH:28]=[N:27][C:26]3[C:21]2=[N:22][C:23]([NH:31][C:32]([C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)([C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[N:24][C:25]=3[O:29][CH3:30])[O:13][C@@H:12]1[CH2:11][O:10][C:9]([C:61]1[CH:66]=[CH:65][C:64]([O:67][CH3:68])=[CH:63][CH:62]=1)([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)[O:76][CH2:75][C:72]1[CH:73]=[CH:74][CH:69]=[CH:70][CH:71]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 86658528HCID 86658528, compound

Product 1

HCID 86658527HCID 86658527, compoundYield 94.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of nucleoside 3 (2.52 g, 2.75 mmol) in anhydrous DCM (8 mL) was added DMAP (1.01 g, 8.2 mmol) and the solution was cooled at 0° C. in an ice-water bath. Cbz-Cl (0.77 g, 4.2 mmol) was added via a syringe to the mixture and resulted in a cloudy reaction mixture. The mixture was stirred at room temperature for 24 hours and sat. NaHCO3 (10 mL) was added. The mixture was partitioned in DCM and water. The organic layer was dried over Na2SO4 and concentrated to a white foam solid. The residue was purified via column chromatography (10˜60% EtOAc in hexanes) to afford 2.74 g product, 4, as a white foam solid (yield, 95%). 1H-NMR (CDCl3): δ 7.87 (s, 1H), 7.41-7.16 (m, 24H), 6.79-6.75 (m 8H), 6.28 (s, 1H), 5.65 (br, 1H), 5.15 (s, 2H), 4.28 (d, 1 H), 3.79-3.71 (m, 15H), 3.55-3.52 (m, 1H), 3.39-3.36 (m, 1H), 0.93 (br, 3H).

Workup

  1. customresulted in a cloudy reaction mixture
  2. customThe mixture was partitioned in DCM
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated to a white foam solid
  5. customThe residue was purified via column chromatography (10˜60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-26c7ef46ab084bdcbb7e3be0114e1d76
Source dataset
uspto-grants-2013_10
Patent number
US08563530B2

Reaction notes

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