Benzyl Bromide → (1R,3S)-1-benzyl 3-tert-butyl 2,2-dimethylcyclobutane-1,3-dicarboxylate

HRID 2179741Notes

Reaction equation

HRID 2179741 reaction equation
[C:1]([O:5][C:6]([C@H:8]1[CH2:11][C@@H:10]([C:12]([OH:14])=[O:13])[C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:17]1[CH:22]=[CH:21][C:20]([CH2:23]Br)=[CH:19][CH:18]=1>CN(C=O)C.C(OCC)(=O)C>[CH3:15][C:9]1([CH3:16])[C@@H:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:11][C@H:10]1[C:12]([O:14][CH2:23][C:20]1[CH:21]=[CH:22][CH:17]=[CH:18][CH:19]=1)=[O:13]

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 21576611(1R,3S)-3-[(tert-Butoxy)carbonyl]-2,2-dimethylcyclobutane-1-carboxylic acid

Product 1

HCID 66859968(1R,3S)-1-benzyl 3-tert-butyl 2,2-dimethylcyclobutane-1,3-dicarboxylateYield 53.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (1R,3S)-3-(tert-butoxycarbonyl)-2,2-dimethylcyclobutanecarboxylic acid (step 2, 0.200 g) in DMF (5 ml) Cs2CO3 (0.371 g) was added at about 0° C. under nitrogen atmosphere. After 30 minutes, BnBr (0.11 ml) was added by drop wise to the reaction mixture and stirred for about 2 hours at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was washed with brine, dried over MgSO4 and concentrated under reduced pressure to give crude product which upon column chromatography afforded the title compound (150 mg, 53.9% Yield). 1H NMR (300 MHz, CDCl3): δ 7.37-7.34 (5H, m), 5.12 (2H, d, J=3.9 Hz), 2.80 (1H, t, J=8.1 Hz), 2.768-2.52 (2H, m), 2.0 (1H, m), 1.44 (9H, m), 1.32 (3H, s), 0.953 (3H, s); Mass: [M+Na]+ 341.2 (100%).

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. washwashed with water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customto give crude product which upon column chromatography

Sources & evidence

ORD record
ord-ef4aace7c048490d811b3f9575a4659f
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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