1,2-Dichloroethane → Tert-butyl[1-(3-butoxy-3-o-tolylazetidine-1-carbonyl)-2-hydroxy-2-(4-methoxy-phenyl)ethyl]carbamate

HRID 540424Notes

Reaction equation

HRID 540424 reaction equation
C(Cl)CCl.[C:5]([O:9][C:10]([NH:12][CH:13]([CH:17]([OH:26])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:14]([OH:16])=O)=[O:11])([CH3:8])([CH3:7])[CH3:6].FC(F)(F)C(O)=O.[CH2:34]([O:38][C:39]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[CH3:49])[CH2:42][NH:41][CH2:40]1)[CH2:35][CH2:36][CH3:37].C1C=NC2N(O)N=NC=2C=1.[OH-].[Na+]>CN(C)C1C=CN=CC=1.ClCCl>[C:5]([O:9][C:10](=[O:11])[NH:12][CH:13]([C:14]([N:41]1[CH2:40][C:39]([O:38][CH2:34][CH2:35][CH2:36][CH3:37])([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[CH3:49])[CH2:42]1)=[O:16])[CH:17]([OH:26])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)([CH3:6])([CH3:7])[CH3:8]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 14798Sodium HydroxideHCID 181649HOAtHCID 141105142-{[(Tert-butoxy)carbonyl]amino}-3-hydroxy-3-(4-methoxyphenyl)propanoic acidHCID 669880653-Butoxy-3-o-tolylazetidine trifluoroacetate

Product 1

HCID 131731976Tert-butyl[1-(3-butoxy-3-o-tolylazetidine-1-carbonyl)-2-hydroxy-2-(4-methoxy-phenyl)ethyl]carbamateYield 87%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

740 mg (3.5 mmol) of EDC and 1.2 g (9.6 mmol) of 4-dimethylaminopyridine are added to a solution of 1 g (3.2 mmol) of 2-tert-butoxycarbonylamino-3-hydroxy-3-(4-methoxyphenyl)propanoic acid, 1.1 g (3.5 mmol) of 3-butoxy-3-o-tolylazetidine trifluoroacetate and 480 mg (3.5 mmol) of HOAT in 10 ml of dichloromethane cooled to 0° C. After stirring for 24 hours at ambient temperature, the reaction medium is treated with a 1N aqueous solution of sodium hydroxide and then extracted with ethyl acetate. The organic phase is washed successively with a 1N aqueous solution of hydrochloric acid and water, and then dried over magnesium sulphate, filtered and concentrated. The residue obtained is purified by silica gel chromatography (eluent: 60/40 heptane/ethyl acetate). 1.4 g of tert-butyl[1-(3-butoxy-3-o-tolylazetidine-1-carbonyl)-2-hydroxy-2-(4-methoxyphenyl)ethyl]carbamate are obtained in the form of a colourless oil with a yield of 87%.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase is washed successively with a 1N aqueous solution of hydrochloric acid and water
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue obtained
  7. customis purified by silica gel chromatography (eluent: 60/40 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-fb57c60bef594f73931151b431d1647d
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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