Acetic Acid → 1,1-Dimethylethyl 3-[[[4-(methoxycarbonyl)phenyl]methyl]amino]-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 16502

Reaction equation

HRID 16502 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@@H:12]2[CH2:13][C:14]([CH2:16][C@H:9]1[CH2:10][CH2:11]2)=O)=[O:7])([CH3:4])[CH3:3].[NH2:17][CH2:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[CH3:26][O:25][C:23]([C:22]1[CH:27]=[CH:28][C:19]([CH2:18][NH:17][CH:14]2[CH2:16][CH:9]3[N:8]([C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7])[CH:12]([CH2:11][CH2:10]3)[CH2:13]2)=[CH:20][CH:21]=1)=[O:24]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 571728Methyl 4-(aminomethyl)benzoateHCID 688612tert-butyl (1R,5S)-3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 684901201,1-Dimethylethyl 3-[[[4-(methoxycarbonyl)phenyl]methyl]amino]-8-azabicyclo[3.2.1]octane-8-carboxylateYield 88.2%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of N-Boc nortropinone (2.4 g, 10.9 mmol) and methyl 4-aminomethylbenzoate (1.6 g, 10.9 mmol) in dichloroethane (20 mL) was stirred as acetic acid (0.85 g, 14.2 mmol) was added. After 1 hour, sodium triacetoxyborohydride (2.7 g, 13.1 mmol) was added and the reaction was stirred for 17 hours. The reaction was treated with a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate (2×). The combined organic extracts were dried and concentrated. Purification by flash chromatography on silica gel using a gradient of ethyl acetate in hexane gave 3.6 g of 1,1-dimethylethyl 3-[[[4-(methoxycarbonyl)phenyl]methyl]amino]-8-azabicyclo[3.2.1]octane-8-carboxylate.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate (2×)
  3. customThe combined organic extracts were dried
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel using a gradient of ethyl acetate in hexane

Sources & evidence

ORD record
ord-a78a28ccfb4340a9954795ea6c536f8c
Source dataset
uspto-grants-2010_06
Patent number
US07737145B2

Linked notes

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