1,2-Dichloroethane → (1-Carbamoyl-spiro[2.5]oct-1-ylmethyl)-carbamic acid tert-butyl ester

HRID 1297226Notes

Reaction equation

HRID 1297226 reaction equation
C[O:2][C:3]([C:5]1([CH2:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:7]2([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:6]1)=O.C1C=CC2N(O)N=[N:28]C=2C=1.CN1CCOCC1.C(Cl)CCl.[OH-].[NH4+]>C1COCC1>[C:18]([O:17][C:15](=[O:16])[NH:14][CH2:13][C:5]1([C:3](=[O:2])[NH2:28])[C:7]2([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:6]1)([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 112318021-(Tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid methyl ester

Product 1

HCID 69515965(1-Carbamoyl-spiro[2.5]oct-1-ylmethyl)-carbamic acid tert-butyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid methyl ester (17.9 g, 63.2 mmol) in THF (700 mL) was added HOBT (9.00 g, 66.4 mmol), 4-methylmorpholine (7.3 mL, 66.4 mmol) followed by EDC (13.9 g, 72.7 mmol). The solution was stirred for 2 hours and then concentrated ammonium hydroxide (8.5 mL, 126 mmol) was added. The mixture was stirred for 18 hours and then the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate and half saturated potassium hydrogen sulfate. An emulsion occurred but the layers were separable. The organic layer was washed with half saturated potassium hydrogen sulfate (2 times) and brine. The organic layer was filtered to remove the emulsified solid. The organic layer was dried over sodium sulfate and filtered. Hexane was added to the filtrate to induce crystallization. The precipitate was isolated by vacuum filtration, washed with hexane and dried in a vacuum oven to give 16.2 g (91%) of (1-carbamoyl-spiro[2.5]oct-1-ylmethyl)-carbamic acid tert-butyl ester as a white solid: 1H NMR (300 MHz, CDCl3) δ 0.65 (d, J=5.0 Hz, 1H), 1.17 (d, J=5.0 Hz, 1H), 1.43(s, 9H), 1.4-1.5 (m, 4H), 1.7-1.7 (m, 6H), 3.37 (dd, J=6.0, 14.0 Hz, 1H), 3.60 (dd, J=6.0, 14.0 Hz, 1H), 5.0 (s, 1H), 5.38 (s, 1H), 6.1 (s, 1H); MS (APCI) m/z 283 [M+H]+.

Workup

  1. stirringThe mixture was stirred for 18 hours
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was partitioned between ethyl acetate and half saturated potassium hydrogen sulfate
  4. washThe organic layer was washed with half saturated potassium hydrogen sulfate (2 times) and brine
  5. filtrationThe organic layer was filtered
  6. customto remove the emulsified solid
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. additionHexane was added to the filtrate
  10. customcrystallization
  11. customThe precipitate was isolated by vacuum filtration
  12. washwashed with hexane
  13. customdried in a vacuum oven

Sources & evidence

ORD record
ord-ae5d12bf68f34757864c3944875aa315
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

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