4-(5,5-Dimethyl-1,3-dioxan-2-yl)butanal → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[[4-(5,5-dimethyl-1,3-dioxan-2-yl)butyl](ethyl)amino]-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one

HRID 505289Notes

Reaction equation

HRID 505289 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[NH:31][CH2:32][CH3:33])[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:37][C:38]1([CH3:49])[CH2:43][O:42][CH:41]([CH2:44][CH2:45][CH2:46][CH:47]=O)[O:40][CH2:39]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.CCOC(C)=O>[F:36][C:2]([F:1])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:28])([F:29])[F:30])[CH:23]=[CH:22][C:21]=3[N:31]([CH2:47][CH2:46][CH2:45][CH2:44][CH:41]3[O:40][CH2:39][C:38]([CH3:37])([CH3:49])[CH2:43][O:42]3)[CH2:32][CH3:33])[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

6

Reactant 3

HCID 27347694-(5,5-Dimethyl-1,3-dioxan-2-yl)butanalHCID 5049666Sodium triacetoxyborohydrideHCID 24896494(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(ethylamino)-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 24896196(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[[4-(5,5-dimethyl-1,3-dioxan-2-yl)butyl](ethyl)amino]-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(ethylamino)-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one (68.2 mg, 0.129 mmol) in dichloroethane (2 mL) was added 4-(5,5-dimethyl-1,3-dioxan-2-yl)butanal (119 mg, 0.643 mmol) and NaBH(OAc)3 (136 mg, 0.643 mmol). The reaction was stirred at room temperature for 72 hours and then diluted with EtOAc (30 mL), quenched with saturated NH4Cl solution (10 mL), and washed with water and brine (10 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (0 to 25% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[[4-(5,5-dimethyl-1,3-dioxan-2-yl)butyl](ethyl)amino]-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.62 (25% EtOAc/hexanes). LCMS=701.3 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ7.97 (s, 1H), 7.85 (s, 2H), 7.23-7.19 (m, 3H), 5.79 (d, J=8.1 Hz, 1H), 4.79 (d, J=16.0 Hz, 1H), 4.62 (d, J=16.0 Hz, 1H), 4.43 (t, J=4.9 Hz, 1H), 4.11-4.01 (m, 1H), 3.61 (d, J=1.1 Hz, 2H), 3.44 (d, J=10.8 Hz, 2H), 3.06-3.00 (m, 4H), 1.71-1.41 (m, 6H), 1.12 (s, 3H), 1.05-1.01 (t, J=7.0 Hz, 3H), 0.77 (s, 3H), 0.74 (d, J=6.6 Hz, 3H).

Workup

  1. customquenched with saturated NH4Cl solution (10 mL)
  2. washwashed with water and brine (10 mL each)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography on silica gel (0 to 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-53286d1a47ef40209c492e4595124f19
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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