1,2-Dichloroethane → tert-Butyl 5-((5-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)isoindolin-2-yl)methyl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate

HRID 710470Notes

Reaction equation

HRID 710470 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]4)[N:14]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2].[CH:34]([C:36]1([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:41][O:40][C:39]([CH3:43])([CH3:42])[O:38][CH2:37]1)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].ClCCCl>C(O)(C(F)(F)F)=O.C(Cl)Cl.CCO.CCOC(C)=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[CH2:23][N:22]([CH2:34][C:36]3([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH2:41][O:40][C:39]([CH3:42])([CH3:43])[O:38][CH2:37]3)[CH2:21]4)[N:14]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 24754730Tert-butyl (5-formyl-2,2-dimethyl-1,3-dioxan-5-yl)carbamateHCID 86661809tert-Butyl 5-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)isoindoline-2-carboxylate

Product 1

HCID 86661810tert-Butyl 5-((5-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)isoindolin-2-yl)methyl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamateYield 63.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A mixture of the product of Step E (0.084 g; 0.186 mmol) in 60% TFA/CH2Cl2 (1.5 ml) was stirred for 5 min at room temperature under N2, then diluted to 4 ml with EtOH, stirred for additional 15 min and evaporated to dryness under reduced pressure. To it, tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate (0.05 g; 0.193 mmol) was added followed by NaBH(OAc)3 (0.13 g; 0.58 mmol) and 1,2-dichloroethane (1.5 ml). The resulting mixture was stirred for 1 h at room temperature, diluted to 15 ml with EtOAc, washed with 10% NaOH (2×5 ml), brine, dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness. The residue was purified by FCC (SiO2; CH2Cl2:EtOAc 8:2) to give the title compound (0.07 g; 63%) as off white foam. 1H-NMR (CDCl3) 1.38-1.61 (m, 21H); 3.21 (s, 2H); 3.82 (d, 2H, J=12 Hz); 4.05-4.24 (m, 10H); 4.98 (broad s, 1H); 6.97 (d, 1H, J=9 Hz); 7.2-7.3 (m, 1H+CDCl3); 7.66 (d, 1H, J=3 Hz); 7.78 (dd, 1H, J=3, 6 Hz); 7.96-8.02 (m, 2H).

Workup

  1. stirringstirred for additional 15 min
  2. customevaporated to dryness under reduced pressure
  3. stirringThe resulting mixture was stirred for 1 h at room temperature
  4. washwashed with 10% NaOH (2×5 ml), brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customfiltrate evaporated to dryness
  8. customThe residue was purified by FCC (SiO2; CH2Cl2:EtOAc 8:2)

Sources & evidence

ORD record
ord-1dc4c9467a6247c396a471dca6760953
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

Loading…