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

HRID 630336Notes

Reaction equation

HRID 630336 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][CH:13]2[CH2:19][CH:18]3[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:15]([CH2:16][CH2:17]3)[CH2:14]2)=[CH:7][CH:6]=1)=[O:4].C=O.[C:30](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][N:12]([CH3:30])[CH:13]2[CH2:14][CH:15]3[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:18]([CH2:17][CH2:16]3)[CH2:19]2)=[CH:9][CH:10]=1)=[O:4]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 684901201,1-Dimethylethyl 3-[[[4-(methoxycarbonyl)phenyl]methyl]amino]-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 684902161,1-Dimethylethyl 3-[[[4-(methoxycarbonyl)phenyl]methyl]methylamino]-8-azabicyclo[3.2.1]octane-8-carboxylateYield 76.8%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 3-[[[4-(methoxycarbonyl)phenyl]methyl]amino]-8-azabicyclo[3.2.1]octane-8-carboxylate (2.1 g, 5.7 mmol) and formaldehyde (1 mL of 37% solution in water) in dichloroethane (20 mL) was stirred as acetic acid (0.37 g, 6.9 mmol) and sodium triacetoxyborohydride (1.7 g, 8 mmol) were added. 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 1.7 g of 1,1-dimethylethyl 3-[[[4-(methoxycarbonyl)phenyl]methyl]methylamino]-8-azabicyclo[3.2.1]octane-8-carboxylate.

Workup

  1. additionwere 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-70b858d8b8694b1fa7e95523d2878b33
Source dataset
uspto-grants-2016_04
Patent number
US09315509B2

Reaction notes

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