Methyl 3-hydroxypivalate → HCID 178473241, compound

HRID 506407Notes

Reaction equation

HRID 506407 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:23]([CH2:24][C:25]3[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=3)[N:22]=[N:21][N:20]=2)[CH2:8][C@H:7]1[CH2:39][CH3:40])=[O:5])[CH3:2].[CH3:41][O:42][C:43](=[O:49])[C:44]([CH3:48])([CH3:47])[CH2:45]O.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:23]([CH2:24][C:25]3[CH:30]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:28]=[C:27]([C:35]([F:36])([F:38])[F:37])[CH:26]=3)[N:22]([CH2:45][C:44]([C:43]([O:42][CH3:41])=[O:49])([CH3:48])[CH3:47])[NH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:39][CH3:40])=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 84152Methyl 3-hydroxypivalateHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 86610701HCID 86610701, compound

Product 1

HCID 178473241HCID 178473241, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 11776TriphenylphosphineSolvent

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(tetrazol-5-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (230 mg) is dissolved in tetrahydrofuran (3 ml), and thereto are added 3-hydroxy-2,2-dimethylpropionic acid methyl ester (58 μl), a solution (0.18 ml) of 40% diethyl azodicarboxylate in toluene and triphenylphosphine (121 mg). The mixture is stirred at room temperature for 19 hours, and partitioned by adding water and diethyl ether. The organic layer is washed with saturated brine, then dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→7:3) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[2-(2-methoxycarbonyl-2-methylpropyl)-2H-tetrazol-5-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (243 mg). MS (m/z): 688 [M+H]+.

Workup

  1. custompartitioned
  2. additionby adding water and diethyl ether
  3. washThe organic layer is washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→7:3)

Sources & evidence

ORD record
ord-946f7cc9c2074db48ebce0207c0feea9
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

Loading…