Acetyl chloride → HCID 86654421, compound

HRID 1844317Notes

Reaction equation

HRID 1844317 reaction equation
[CH2:1]([O:8][C:9]([C@:11]1([C:31]2([OH:35])[CH2:34][CH2:33][CH2:32]2)[CH2:15][C@H:14]([N:16]([C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[C@@H:17]2[C@H:22]([O:23][CH3:24])[CH2:21][O:20][CH2:19][CH2:18]2)[CH:13]=[CH:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:45](Cl)(=[O:47])[CH3:46]>CN(C1C=CN=CC=1)C.ClCCl>[C:45]([O:35][C:31]1([C@@:11]2([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])[CH2:15][C@H:14]([N:16]([C:25](=[O:30])[C:26]([F:27])([F:28])[F:29])[C@@H:17]3[C@H:22]([O:23][CH3:24])[CH2:21][O:20][CH2:19][CH2:18]3)[CH:13]=[CH:12]2)[CH2:32][CH2:33][CH2:34]1)(=[O:47])[CH3:46]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 58305861HCID 58305861, compound

Product 1

HCID 86654421HCID 86654421, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3.58 g (7.2 mmol) of 1,5-anhydro-3-{[(1S,4R)-4-[(benzyloxy)carbonyl]-4-(1-hydroxycyclobutyl)cyclopent-2-en-1-yl](trifluoroacetyl)amino}-2,3-dideoxy-4-O-methyl-D-erythro-pentitol 1.6 ml (9.2 mmol) of diisopropylethylamine, and 100 mg (0.82 mmol) of DMAP in 10 mL of dichloromethane was added dropwise 5.1 mL (72 mmol) of acetyl chloride. The solution was stirred at ambient temperature for 18 h, then cooled in ice and quenched with aqueous NaHCO3. The aqueous phase was extracted with additional dichloromethane, and the combined organic phases dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography of the residue on silica using 8-10% ethyl acetate in dichloromethane provided 2.63 g (68%) of the title compound as a viscous yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35-1.48 (m, 1H) 1.54-1.61 (m, 1H) 1.82-1.94 (m, 1H) 1.88 (s, 3H) 2.17-2.26 (m, 1H) 2.34 (dd, J=1.47, 9.9 Hz, 1H) 2.43-2.64 (m, 5H) 3.32 (d, J=12.6 Hz, 1H) 3.37-3.43 (m, 1H) 3.43 (s, 3H) 3.46-3.55 (m, 1H) 3.84-3.94 (m, 1H) 4.09-4.15 (m, 1H) 4.19 (d, J=13.0 Hz, 1H) 4.98-5.05 (m, 1H) 5.08 (d, J=12.3 Hz, 1H) 5.23 (d, J=12.3 Hz, 1H) 5.75 (dd, J=5.8, 2.0 Hz, 1H) 6.16 (dd, J=5.8, 2.4 Hz, 1H) 7.28-7.43 (m, 5H). TLC Rf 0.39 (10% ethyl acetate-dichloromethane). LC-MS ES+ 540.2.

Workup

  1. temperaturecooled in ice
  2. customquenched with aqueous NaHCO3
  3. extractionThe aqueous phase was extracted with additional dichloromethane
  4. dry with materialthe combined organic phases dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-45447ca0d05d4aa8943467e0f440c23f
Source dataset
uspto-grants-2015_02
Patent number
US08946413B2

Reaction notes

Loading…