Sodium Hydroxide → Tert-butyl[3-(7-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]carbamate

HRID 2078442Notes

Reaction equation

HRID 2078442 reaction equation
Cl.Cl.[CH2:3]([N:10]1[CH2:17][CH:16]2[O:18][CH:12]([CH2:13][NH:14][CH2:15]2)[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[OH-].[Na+].CC1C=C(C)C=C(C)C=1S(O[CH2:34][CH2:35][CH2:36][NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])(=O)=O>C1(C)C=CC=CC=1>[C:41]([O:40][C:38](=[O:39])[NH:37][CH2:36][CH2:35][CH2:34][N:14]1[CH2:15][CH:16]2[O:18][CH:12]([CH2:11][N:10]([CH2:3][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:17]2)[CH2:13]1)([CH3:44])([CH3:43])[CH3:42]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 185403703-(Phenylmethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane, hydrochloride (1:2)HCID 866280503-(tert-Butyloxycarbonylamino)propyl 2,4,6-trimethylbenzenesulfonate

Product 1

HCID 15980224Tert-butyl[3-(7-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]carbamateYield 90.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

To 3-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]nonane dihydrochloride (25.08 g, 86.12 mmol; see Preparation O above) was added 2.5 M sodium hydroxide (115 mL). 3-(tert-Butyloxycarbonylamino)propyl 2,4,6-trimethylbenzenesulfonate (32.35 g, 90.50 mmol; see Preparation L above) and toluene (65 mL) were then added and the reaction mixture heated at 65° C. for 12 hours. The phases were separated at 65° C. and the lower (aqueous) layer discarded. The organic phase was re-heated to 65° C. and then extracted with 10% w/w aqueous citric acid (125 mL). The phases were separated and the upper (organic) phase discarded. To the aqueous citric acid phase was added isopropyl acetate (150 mL) and 5 M sodium hydroxide (75 mL). The resulting mixture was stirred at room temperature for 15 minutes. The phases were separated and the lower (aqueous) phase discarded. The resulting organic phase was dried (MgSO4), filtered and the solvent removed in vacuo to give the title compound as a colourless oil (29.13 g, 77.60 mmol, 90%).

Workup

  1. customThe phases were separated at 65° C.
  2. temperatureThe organic phase was re-heated to 65° C.
  3. extractionextracted with 10% w/w aqueous citric acid (125 mL)
  4. customThe phases were separated
  5. additionTo the aqueous citric acid phase was added isopropyl acetate (150 mL) and 5 M sodium hydroxide (75 mL)
  6. customThe phases were separated
  7. dry with materialThe resulting organic phase was dried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-25ad5fa932a4471a9815abb80ea50374
Source dataset
uspto-grants-2011_04
Patent number
US07928225B2

Reaction notes

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