Benzyl Bromide → (1S,3R)-benzyl 3-acetyl-2,2-dimethylcyclobutanecarboxylate

HRID 2179726Notes

Reaction equation

HRID 2179726 reaction equation
[C:1]([C@@H:4]1[CH2:7][C@H:6]([C:8]([OH:10])=[O:9])[C:5]1([CH3:12])[CH3:11])(=[O:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH:19]1[CH:24]=[CH:23][C:22]([CH2:25]Br)=[CH:21][CH:20]=1>CN(C=O)C.CCOC(C)=O>[C:1]([C@@H:4]1[CH2:7][C@H:6]([C:8]([O:10][CH2:25][C:22]2[CH:23]=[CH:24][CH:19]=[CH:20][CH:21]=2)=[O:9])[C:5]1([CH3:12])[CH3:11])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 10630987(1S,3R)-3-acetyl-2,2-dimethylcyclobutane-1-carboxylic acid

Product 1

HCID 58111012(1S,3R)-benzyl 3-acetyl-2,2-dimethylcyclobutanecarboxylateYield 61.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of (1S,3R)-3-acetyl-2,2-dimethylcyclobutanecarboxylic acid (6.0 g, 35.29 mmol) in DMF (20 ml) at 0° C., Cs2CO3 (13.8 g, 42.34 mmol) followed by BnBr (5.06 ml, 42.34 mmol) were added slowly portion wise. The reaction was stirred at room temperature for about 2 hours. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with EtOAc (100 ml) and washed with water (50 ml), brine (50 ml) and dried with Na2SO4. The solvent was evaporated and purified by silica gel column (60-120, elution 4% EtOAc in hexane) to afford title compound as a pale yellow syrup. Wt: 5.6 g; Yield: 61.5%; 1H NMR (300 MHZ, CDCl3): δ 7.42-7.31 (m, 5H), 5.13 (s, 2H), 2.93-2.81 (m, 2H), 2.68 (q, 1H, J=10.5 Hz,), 2.05 (s, 3H), 1.97-1.88 (m, 1H), 1.43 (s, 3H), 0.87 (s, 3H); Mass: [M+1]+ 261 (20%), [M+Na]+ 283 (87%); IR (KBr, cm−1): 2889, 1732, 1708, 1498, 1456, 1329, 1279, 1183, 1027, 954, 752, 698.

Workup

  1. customat 0° C.
  2. additionwere added slowly portion wise
  3. customAfter completion of the reaction (monitored by TLC)
  4. washwashed with water (50 ml), brine (50 ml)
  5. dry with materialdried with Na2SO4
  6. customThe solvent was evaporated
  7. custompurified by silica gel column (60-120, elution 4% EtOAc in hexane)

Sources & evidence

ORD record
ord-1abef5ae2eba443da0c6ff77ab884581
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

Loading…