Acetic Anhydride → HCID 59643928, compound

HRID 2252430Notes

Reaction equation

HRID 2252430 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10](=[O:18])[C@@H:9]2[CH2:19][CH2:20][C@H:21]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[C:4]([OH:37])[CH:3]=1.[C:38](OC(=O)C)(=[O:40])[CH3:39]>ClCCl.CN(C)C1C=CN=CC=1>[C:38]([O:37][C:4]1[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][C:5]=1[C@@H:8]1[C@@H:9]([CH2:19][CH2:20][C@H:21]([O:29][Si:30]([C:33]([CH3:34])([CH3:36])[CH3:35])([CH3:32])[CH3:31])[C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[C:10](=[O:18])[N:11]1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)(=[O:40])[CH3:39]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 59643934(3R,4S)-4-(4-bromo-2-hydroxyphenyl)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-1-phenylazetidin-2-one

Product 1

HCID 59643928HCID 59643928, compoundYield 78.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(3R,4S)-4-(4-Bromo-2-hydroxyphenyl)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-1-phenylazetidin-2-one (293 mg, 0.50 mmol) was dissolved in anhydrous dichloromethane (3 mL). 4-Dimethylaminopyridine (183 mg, 1.5 mmol) was added followed by acetic anhydride (280 μL, 302 mg, 3.0 mmol). After 1 h the reaction was filtered through a plug of silica gel and eluted with dichloromethane. The solvent was concentrated, azeotroped with toluene and purified by chromatography (40 g silica gel, 1% to 85% ethyl acetate-hexane) to afford 5-bromo-2-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}phenyl acetate (245 mg, 78% yield); Rf 0.47 (1:4 ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ 7.38-7.16 (m, 9H), 7.14-6.94 (m, 3H), 4.69 (t, J=5.4 Hz, 1H), 4.64 (d, J=2.3 Hz, 1H), 3.06 (ddd, J=4.7, 2.3, 2.2 Hz, 1H), 2.30 (s, 3H), 1.97-1.78 (m, 4H), 0.89 (s, 9H), 0.032 (s, 3H), −0.14 (s, 3H) ppm; MS [M−OSi(CH3)2C(CH3)3]+ 493.8.

Workup

  1. filtrationAfter 1 h the reaction was filtered through a plug of silica gel
  2. washeluted with dichloromethane
  3. concentrationThe solvent was concentrated
  4. customazeotroped with toluene
  5. custompurified by chromatography (40 g silica gel, 1% to 85% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-0f09b9780c6f4de197d7aefac067c093
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

Loading…