Acetic Acid → 9-(Tert-butoxycarbonyl)-4-(2,2,2-trifluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2-carboxylic acid

HRID 712956Notes

Reaction equation

HRID 712956 reaction equation
[F:1][C:2]([F:27])([F:26])[CH2:3][N:4]1[CH2:9][C:8]2([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[O:7][CH:6]([C:22]([O:24]C)=[O:23])[CH2:5]1.[Li+].[OH-].C(O)(=O)C.C1(C)C=CC=CC=1>CO.O>[C:18]([O:17][C:15]([N:12]1[CH2:11][CH2:10][C:8]2([O:7][CH:6]([C:22]([OH:24])=[O:23])[CH2:5][N:4]([CH2:3][C:2]([F:27])([F:1])[F:26])[CH2:9]2)[CH2:14][CH2:13]1)=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 1140TolueneHCID 3939Lithium HydroxideHCID 682913439-Tert-butyl 2-methyl 4-(2,2,2-trifluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2,9-dicarboxylate

Product 1

HCID 682914539-(Tert-butoxycarbonyl)-4-(2,2,2-trifluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2-carboxylic acidYield 77.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

9-Tert-butyl 2-methyl 4-(2,2,2-trifluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2,9-dicarboxylate (197 mg, 0.48 mmol) was dissolved in MeOH (1 mL)/H2O (1 mL), followed by the addition of LiOH (46 mg, 1.92 mmol) and the reaction mixture was stirred for 2 hours at room temperature. The solvent was removed in vacuo and the residue was dissolved in water (2 mL) and cooled to 0° C., then acetic acid (115 mg, 109 μL, 1.92 mmol) was added dropwise (pH=5). The product was partitioned between EtOAc/water, the layers were separated and the aqueous layer was extracted once more with EtOAc. The organics were dried over Na2SO4, filtered and concentrated in vacuo to yield an oil. The oil was co-evaporated twice with toluene and dried under high vacuum to yield 9-(tert-butoxycarbonyl)-4-(2,2,2-trifluoroethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-2-carboxylic acid (142 mg, 77%) as a white foam. ESI-MS m/z calc. 382.4. found 383.5 (M+1)+; Retention time: 1.58 minutes (3 min run).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in water (2 mL)
  3. temperaturecooled to 0° C.
  4. customThe product was partitioned between EtOAc/water
  5. customthe layers were separated
  6. extractionthe aqueous layer was extracted once more with EtOAc
  7. dry with materialThe organics were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield an oil
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-471118303907471a9088c32fa3883313
Source dataset
uspto-grants-2015_11
Patent number
US09181273B2

Reaction notes

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