(+)-8-Phenylmenthol → (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 5-(3-bromo-4-fluorophenyl)-4,6-dioxo-1,3,4,5,6,7,8,9-octahydro-2H-cyclopenta[b][1,7]naphthyridine-2-carboxylate

HRID 478262

Reaction equation

HRID 478262 reaction equation
C([N:8]1[CH2:17][C:16]2[NH:15][C:14]3[CH2:18][CH2:19][C:20](=[O:21])[C:13]=3[CH:12]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Br:29])[CH:23]=3)[C:11]=2[C:10](=[O:30])[CH2:9]1)C1C=CC=CC=1.Cl[C:32]([O:34][CH:35]1[CH:40]([C:41]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([CH3:43])[CH3:42])[CH2:39][CH2:38][CH:37]([CH3:50])[CH2:36]1)=[O:33].C1(C(C)(C)C2CCC(C)CC2O)C=CC=CC=1>C1COCC1>[Br:29][C:24]1[CH:23]=[C:22]([CH:12]2[C:11]3[C:10](=[O:30])[CH2:9][N:8]([C:32]([O:34][C@@H:35]4[CH2:36][C@H:37]([CH3:50])[CH2:38][CH2:39][C@H:40]4[C:41]([CH3:42])([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[CH3:43])=[O:33])[CH2:17][C:16]=3[NH:15][C:14]3[CH2:18][CH2:19][C:20](=[O:21])[C:13]2=3)[CH:27]=[CH:26][C:25]=1[F:28]

Participants

5

Reactant 3

HCID 577105(+)-8-PhenylmentholHCID 113288132-benzyl-5-(3-bromo-4-fluorophenyl)-2,3,5,7,8,9-hexahydro-1H-cyclopenta[b][1,7]naphthyridine-4,6-dioneHCID 145714908-Phenylmenthol chloroformate

Product 1

HCID 69302932(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 5-(3-bromo-4-fluorophenyl)-4,6-dioxo-1,3,4,5,6,7,8,9-octahydro-2H-cyclopenta[b][1,7]naphthyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the product from Example 5A (1.9 g, 4.0 mmol) in THF (30 mL) was treated with 8-phenylmenthol chloroformate prepared from (−)-8-phenylmenthol as described in (Yamamoto, Y., J.Amer.Chem.Soc. (1992), 114, 121-125) (1.45 g, 4.92 mmol) in THF (10 mL), stirred for 3 days at ambient temperature and partitioned between aqueous sodium bicarbonate and methylene chloride. The organic layer was separated, dried with sodium sulfate, filtered and concentrated to provide a mixture of diastereomeric carbamates. The diastereomeric mixture was subjected to column chromatography over silica gel (20% hexanes/ethyl acetate) to provide the title compound (0.32 g) as the less polar diastereomer and mixed fractions containing both diastereomers (0.9 g).

Workup

  1. custompartitioned between aqueous sodium bicarbonate and methylene chloride
  2. customThe organic layer was separated
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide

Sources & evidence

ORD record
ord-5f9475acc7f94d3db67c4a8fcfa590fe
Source dataset
uspto-grants-2003_11
Patent number
US06642222B2

Linked notes

Loading…