Dicyclohexylcarbodiimide → 17-Allyl-12-(2-(4-((-)-2-trifluoromethyl-2-methoxy-2-phenylacetoxy)-3-methoxycyclohexyl)-1-methylvinyl)-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo(22.3.1.04,9)octacos-18-ene-2, 3,10,16-tetraone

HRID 330048Notes

Reaction equation

HRID 330048 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]([O:13][CH3:14])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=[O:5].C1(N=C=NC2CCCCC2)CCCCC1.[CH3:32][C@H:33]1[CH2:64][C:63]([CH3:65])=[CH:62][C@@H:61]([CH2:66][CH:67]=[CH2:68])[C:59](=[O:60])[CH2:58][C@H:57]([OH:69])[C@@H:56]([CH3:70])[C@@H:55](/[C:71](/[CH3:82])=[CH:72]/[C@H:73]2[CH2:78][C@@H:77]([O:79][CH3:80])[C@H:76](O)[CH2:75][CH2:74]2)[O:54][C:52](=[O:53])[C@H:51]2[N:46]([CH2:47][CH2:48][CH2:49][CH2:50]2)[C:44](=[O:45])[C:42](=[O:43])[C@:40]2([OH:83])[O:41][C@@H:36]([C@@H:37]([O:85][CH3:86])[CH2:38][C@H:39]2[CH3:84])[C@@H:35]([O:87][CH3:88])[CH2:34]1>C(OCC)(=O)C.CN(C1C=CN=CC=1)C.C(OCC)C>[CH2:66]([CH:61]1[CH:62]=[C:63]([CH3:65])[CH2:64][CH:33]([CH3:32])[CH2:34][CH:35]([O:87][CH3:88])[CH:36]2[O:41][C:40]([OH:83])([CH:39]([CH3:84])[CH2:38][CH:37]2[O:85][CH3:86])[C:42](=[O:43])[C:44](=[O:45])[N:46]2[CH:51]([CH2:50][CH2:49][CH2:48][CH2:47]2)[C:52](=[O:53])[O:54][CH:55]([C:71]([CH3:82])=[CH:72][CH:73]2[CH2:74][CH2:75][CH:76]([O:5][C:4](=[O:6])[C:3]([C:2]([F:15])([F:16])[F:1])([O:13][CH3:14])[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:77]([O:79][CH3:80])[CH2:78]2)[CH:56]([CH3:70])[CH:57]([OH:69])[CH2:58][C:59]1=[O:60])[CH:67]=[CH2:68]

Participants

7

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 86531Mosher's acidHCID 445643Tacrolimus

Product 1

HCID 5722415617-Allyl-12-(2-(4-((-)-2-trifluoromethyl-2-methoxy-2-phenylacetoxy)-3-methoxycyclohexyl)-1-methylvinyl)-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo(22.3.1.04,9)octacos-18-ene-2, 3,10,16-tetraone

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (-)-2-trifluoromethyl-2-methoxy-2-phenylacetic acid (51 mg) in ethyl acetate (10 ml) was added at room temperature N,N'-dicyclohexylcarbodiimide (47 mg). After stirring for 1.5 hours at room temperature, then the FR-900506 substance (25.0 mg) and 4-(N,N-dimethylamino)-pyridine (11 mg) were added, followed by stirring at room temperature for 3.5 hours. The resulting solution was concentrated to provide a residue, which was taken up in diethyl ether and then washed successively with hydrochloric acid, an aqueous sodium hydrogen carbonate and an aqueous sodium chloride. The organic layer was dried over sodium sulfate and concentrated to provide a residue, which was chromatographed on silica gel (developing solvent: dichloromethane and diethyl ether, 10:1 v/v) to give 17-allyl-12-[2-[4-[(-)-2-trifluoromethyl-2-methoxy-2phenylacetoxy]-3-methoxycyclohexyl]-1-methylvinyl]-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (6.5 mg) and 17-allyl-14-[(-)- 2-trifluoromethyl-2-methoxy-2-phenylacetoxy]-12-[2-[4-(-)-2-trifluoromethyl-2-methoxy-2-phenylacetoxy]-3-methoxycyclohexyl]3-methylvinyl]-1-hydroxy-23,25 -dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.04,9 octacos-18-ene-2,3,10,16-tetraone (20.2 mg).

Workup

  1. stirringby stirring at room temperature for 3.5 hours
  2. concentrationThe resulting solution was concentrated
  3. customto provide a residue, which
  4. washwashed successively with hydrochloric acid
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. customto provide a residue, which
  8. customwas chromatographed on silica gel (developing solvent: dichloromethane and diethyl ether, 10:1 v/v)

Sources & evidence

ORD record
ord-a213700641a24844b64571256c1b0b5a
Source dataset
uspto-grants-1990_01
Patent number
US04894366

Reaction notes

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