Sodium hydride → Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-{[9-(tert-butyldimethyl-silanyloxy)nonyl]methylamino}bicyclo[2.2.1]hept-2-ylester

HRID 1670897Notes

Reaction equation

HRID 1670897 reaction equation
[H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]([CH3:29])[C@H:21]1[C@H:25]2[CH2:26][CH2:27][C@@H:22]1[C@H:23]([OH:28])[CH2:24]2)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].C([O:32][C:33](=O)[C:34]([OH:45])([C:40]1[S:41][CH:42]=[CH:43][CH:44]=1)[C:35]1[S:36][CH:37]=[CH:38][CH:39]=1)C.[Cl-].[NH4+]>C1(C)C=CC=CC=1.CCOCC>[C:6]([Si:3]([CH3:4])([CH3:5])[O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]([CH3:29])[C@H:21]1[C@H:25]2[CH2:26][CH2:27][C@@H:22]1[C@H:23]([O:28][C:33](=[O:32])[C:34]([OH:45])([C:35]1[S:36][CH:37]=[CH:38][CH:39]=1)[C:40]1[S:41][CH:42]=[CH:43][CH:44]=1)[CH2:24]2)([CH3:9])([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 12723738Ethyl 2-hydroxy-2,2-DI(thiophen-2-YL)acetateHCID 67348477(1S,2R,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-ol

Product 1

HCID 67349685Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-{[9-(tert-butyldimethyl-silanyloxy)nonyl]methylamino}bicyclo[2.2.1]hept-2-ylester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

Sodium hydride (254 mg, 60% suspension in mineral oil, 6.35 mmol) was added to a solution of (1S,2R,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-ol (1.01 g, 2.54 mmol) in dry toluene (20 mL) at 0° C. under a nitrogen atmosphere. As soon as the gas evolution subsided hydroxy-di-thiophen-2-yl-acetic acid ethyl ester (817 mg, 3.04 mmol) was added in portions, and when the gas evolution stopped the reaction mixture was heated at 80° C. on a preheated sand bath. After 2.5 h the reaction mixture was poured onto satd ammonium chloride (aq) and ether. The layers were separated, the aqueous layer extracted with ether, and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated to dryness to afford a light brown viscous oil. The crude product was purified by column chromatography over silica gel using a gradient of 1-40% ethyl acetate in DCM as eluent to afford the product as a very light brown viscous oil.

Workup

  1. additionwas added in portions, and when the gas evolution
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with ether
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customto afford a light brown viscous oil
  9. customThe crude product was purified by column chromatography over silica gel using a gradient of 1-40% ethyl acetate in DCM as eluent
  10. customto afford the product as a very light brown viscous oil

Sources & evidence

ORD record
ord-acca2f39cf5f47158b0a72edc402f1ff
Source dataset
uspto-grants-2011_08
Patent number
US07994211B2

Reaction notes

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