Acetone → HCID 57148311, compound

HRID 843430Notes

Reaction equation

HRID 843430 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([O:14][CH2:15][C:16]2[CH:25]=[C:24]([O:26][CH3:27])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[C@@H:11]([C:28]2[CH:33]=[CH:32][C:31]([O:34]CC=C)=[CH:30][CH:29]=2)[C@H:10]([O:38][CH2:39][C@H:40]2[CH2:44][O:43][C:42]([CH3:46])([CH3:45])[O:41]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[BH4-].[Li+].CC(C)=O>O1CCCC1.C(=O)([O-])O.[Na+].CC(O)=O.CC(O)=O.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([O:14][CH2:15][C:16]2[CH:25]=[C:24]([O:26][CH3:27])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[C@@H:11]([C:28]2[CH:29]=[CH:30][C:31]([OH:34])=[CH:32][CH:33]=2)[C@H:10]([O:38][CH2:39][C@H:40]2[CH2:44][O:43][C:42]([CH3:46])([CH3:45])[O:41]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 180AcetoneHCID 11776TriphenylphosphineHCID 4148881Lithium borohydrideHCID 67220305(3S,4R,5R)-4-(4-allyloxy-phenyl)-3-[(S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57148311HCID 57148311, compound

Reagents, catalysts & solvents 3

HCID 4144353Palladium (II) acetateCatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
5 °C

Procedure

0.40 g (0.63 mmol) of (3S,4R,5R)-4-(4-allyloxy-phenyl)-3-[(S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester, 1.4 mg (0.0063 mmol) of palladium-II-acetate and 3.3 mg (0.0126 mmol) of triphenylphosphin were dissolved in 2 ml of tetrahydrofuran. After cooling to 5° C., 21.7 mg (0.947 mmol) of lithiumborohydride were added and the reaction mixture stirred for 4 hours without cooling. Thereafter, the reaction mixture was again cooled to 5° C. and treated with 0.32 ml of acetone, then diluted with 5 ml of saturated sodium hydrogen carbonate solution and extracted twice with 5 ml of ether. The combined organic phases were washed once with a small amount of water, dried over magnesium sulphate, evaporated under reduced pressure and dried in a high vacuum. The thus-obtained crude product was separated on silica gel using a mixture of dichloromethane/ethyl acetate (4/1) as the eluent and yielded 0.343 g (0.578 mmol), 91.5%, (3S,4R,5R)-3-[(4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-4-(4-hydroxy-phenyl)-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester as colorless oil; MS: 594 (M+H)+.

Workup

  1. temperaturewithout cooling
  2. temperatureThereafter, the reaction mixture was again cooled to 5° C.
  3. extractionextracted twice with 5 ml of ether
  4. washThe combined organic phases were washed once with a small amount of water
  5. dry with materialdried over magnesium sulphate
  6. customevaporated under reduced pressure
  7. customdried in a high vacuum
  8. customThe thus-obtained crude product
  9. customwas separated on silica gel using
  10. additiona mixture of dichloromethane/ethyl acetate (4/1) as the eluent

Sources & evidence

ORD record
ord-95c03eb96a734847addce2508fc8f0f6
Source dataset
uspto-grants-2002_04
Patent number
US06376672B1

Reaction notes

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