Dicyclopropylmethoxybenzoyl chloride → (+/-)-Acetic acid (1RS,3RS,4RS)-4-{[1-(3,4-bis-cyclopropylmethoxyphenyl)methanoyl]-amino}-3-(3,4-dimethoxyphenyl)cyclohexyl ester

HRID 1867467Notes

Reaction equation

HRID 1867467 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([O:8][C:9](=[O:11])[CH3:10])[CH2:4][CH:3]1[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=1.[CH:22]1([CH2:25][O:26][C:27]2[CH:28]=[C:29]([CH:33]=[CH:34][C:35]=2[O:36][CH2:37][CH:38]2[CH2:40][CH2:39]2)[C:30](Cl)=[O:31])[CH2:24][CH2:23]1.C1(C(C2CC2)OC2C=CC=CC=2C(Cl)=O)CC1>C(Cl)Cl.N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH:22]1([CH2:25][O:26][C:27]2[CH:28]=[C:29]([C:30]([NH:1][CH:2]3[CH2:7][CH2:6][CH:5]([O:8][C:9](=[O:11])[CH3:10])[CH2:4][CH:3]3[C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)=[O:31])[CH:33]=[CH:34][C:35]=2[O:36][CH2:37][CH:38]2[CH2:39][CH2:40]2)[CH2:24][CH2:23]1

Participants

7

Reactant 3

HCID 17989077Dicyclopropylmethoxybenzoyl chlorideHCID 179890793,4-Bis(cyclopropylmethoxy)benzoyl chlorideHCID 67022805acetic acid (1RS,3RS,4RS)-4-amino-3-(3,4-dimethoxyphenyl)cyclohexyl ester2×

Product 1

HCID 86601277(+/-)-Acetic acid (1RS,3RS,4RS)-4-{[1-(3,4-bis-cyclopropylmethoxyphenyl)methanoyl]-amino}-3-(3,4-dimethoxyphenyl)cyclohexyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

590 mg of (±)-acetic acid (1RS,3RS,4RS)-4-amino-3-(3,4-dimethoxyphenyl)cyclohexyl ester (compound B1) are dissolved in a mixture of 6 ml of methylene chloride and 1.5 ml of pyridine and 10 mg of 4-dimethylaminopyridine are added. A solution of 595 mg of 3,4-dicyclopropylmethoxybenzoyl chloride in methylene chloride is added dropwise and the mixture is stirred for 16 h. Further 140 mg of dicyclopropylmethoxybenzoyl chloride and 10 mg of 4-dimethylaminopyridine are added to complete the reaction. The solvents are removed and the residue is purified by chromatography on silica gel using a mixture of petroleum ether/ethyl acetate/triethylamine in the ratio 5/4/1 as eluent. After concentration of the corresponding eluate fractions, 630 mg (59% of theory) of the title compound are obtained as a colourless foam.

Workup

  1. additionare added
  2. customthe reaction
  3. customThe solvents are removed
  4. customthe residue is purified by chromatography on silica gel using
  5. additiona mixture of petroleum ether/ethyl acetate/triethylamine in the ratio 5/4/1 as eluent

Sources & evidence

ORD record
ord-1ec1c8f310624d0d8cb8bccd072f1dc8
Source dataset
uspto-grants-2009_12
Patent number
US07632844B2

Reaction notes

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