Diisopropylamine → 3-Amino-3-[4-benzyloxy-7-(4-chloro-phenylsulfanyl)-3-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-acrylic acid tert-butyl ester

HRID 989367Notes

Reaction equation

HRID 989367 reaction equation
C([Mg]Br)C.C(NC(C)C)(C)C.[C:12]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:14])[CH3:13].[CH2:20]([O:27][C:28]1[CH:35]=[C:34]2[C:31]([CH2:32][C:33]2([S:38][C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=2)[C:36]#[N:37])=[CH:30][C:29]=1[O:46][CH3:47])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(OCC)C.O1CCCC1>[C:16]([O:15][C:12](=[O:14])[CH:13]=[C:36]([NH2:37])[C:33]1([S:38][C:39]2[CH:40]=[CH:41][C:42]([Cl:45])=[CH:43][CH:44]=2)[CH2:32][C:31]2[C:34]1=[CH:35][C:28]([O:27][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[C:29]([O:46][CH3:47])[CH:30]=2)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 10908tert-Butyl acetateHCID 113956914-Benzyloxy-7-(4-chloro-phenylsulfanyl)-3-methoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 692686913-Amino-3-[4-benzyloxy-7-(4-chloro-phenylsulfanyl)-3-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-acrylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of ethylmagnesium bromide (3.26 mL of a 3M solution in diethyl ether, 9.8 mmol) in anhydrous tetrahydrofuran (10 mL) at 0° C. under nitrogen is added diisopropylamine (2.75 mL, 19.6 mmol). The mixture is stirred at 0° C. for 1 hour. t-Butyl acetate (0.5 mL, 3.6 mmol) and a solution of 1.0 g (2.45 mmol) of 4-benzyloxy-7-(4-chloro-phenylsulfanyl)-3-methoxybicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile in anhydrous tetrahydrofuran (10 mL) are added successively, and the resulting mixture is stirred for an additional hour. The reaction is quenched with aqueous ammonium chloride and the product mixture is extracted with ethyl acetate. The ethyl acetate extract is washed with brine, dried over anhydrous sodium sulfate and passed through a plug of silica to give 3-amino-3-[4-benzyloxy-7-(4-chloro-phenylsulfanyl)-3-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-acrylic acid tert-butyl ester as a clear oil, that solidified upon standing, mp 112-115° C.

Workup

  1. stirringthe resulting mixture is stirred for an additional hour
  2. customThe reaction is quenched with aqueous ammonium chloride
  3. extractionthe product mixture is extracted with ethyl acetate
  4. extractionThe ethyl acetate extract
  5. washis washed with brine
  6. dry with materialdried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-f940d28189d847648d0a18c675b64153
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Reaction notes

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