Trifluoroacetic acid → 6-(4-(Azetidin-3-yloxy)benzyl)-2-oxa-6-azaspiro[3.3]heptane

HRID 1639505Notes

Reaction equation

HRID 1639505 reaction equation
[CH2:1]1[C:4]2([CH2:7][N:6]([CH2:8][C:9]3[CH:26]=[CH:25][C:12]([O:13][CH:14]4[CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15]4)=[CH:11][CH:10]=3)[CH2:5]2)[CH2:3][O:2]1.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+]>ClCCl>[NH:16]1[CH2:17][CH:14]([O:13][C:12]2[CH:25]=[CH:26][C:9]([CH2:8][N:6]3[CH2:5][C:4]4([CH2:1][O:2][CH2:3]4)[CH2:7]3)=[CH:10][CH:11]=2)[CH2:15]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium Carbonate2×HCID 59563505tert-Butyl 3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidine-1-carboxylate

Product 1

HCID 595635036-(4-(Azetidin-3-yloxy)benzyl)-2-oxa-6-azaspiro[3.3]heptaneYield 94.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3A (0.19 g, 0.52 mmol) was dissolved in dichloromethane (20 mL) and TFA (1.95 mL, 26 mmol) was added. The reaction mixture was stirred at room temperature for two hours. K2CO3 (5 g) was added in portions and the mixture was stirred for 20 min. A saturated solution of K2CO3 (aq) was added and the mixture was transferred to a separatory funnel. The layers were separated and the aqueous layer was further extracted several times with dichloromethane. The combined organic solutions were dried (phase separator) and evaporated. There was obtained 128 mg (94%) of 3B as an oil. 1H NMR (500 MHz, CDCl3): δ 3.34 (s, 4H), 3.45 (s, 2H), 3.80 (m, 2H), 3.92 (m, 2H), 4.72 (s, 4H), 4.98 (m, 1H), 6.69 (d, 2H), 7.13 (d, 2H), MS (APCI+) m/z 261 [M+H]+.

Workup

  1. stirringthe mixture was stirred for 20 min
  2. customthe mixture was transferred to a separatory funnel
  3. customThe layers were separated
  4. customThe combined organic solutions were dried (phase separator)
  5. customevaporated

Sources & evidence

ORD record
ord-e86b2d2a475e4ab4972ab8e0f92d3fed
Source dataset
uspto-grants-2012_02
Patent number
US08110566B2

Reaction notes

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