Triethylamine → ((2S,3S)-7-Carbamoyl-1,1-diethyl-3-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-carbamic acid (R)-1-phenyl-ethyl ester

HRID 2369189Notes

Reaction equation

HRID 2369189 reaction equation
[C:1]1([C@H:7]([O:9][C:10](=[O:21])OC2C=CC([N+]([O-])=O)=CC=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl.[NH2:30][C@@H:31]1[C:40]([CH2:43][CH3:44])([CH2:41][CH3:42])[C:39]2[CH:38]=[C:37]([C:45]([NH2:47])=[O:46])[CH:36]=[CH:35][C:34]=2[CH2:33][C@H:32]1[O:48][CH3:49]>CN(C)C=O>[C:1]1([C@H:7]([O:9][C:10](=[O:21])[NH:30][C@@H:31]2[C@@H:32]([O:48][CH3:49])[CH2:33][C:34]3[C:39](=[CH:38][C:37]([C:45](=[O:46])[NH2:47])=[CH:36][CH:35]=3)[C:40]2([CH2:43][CH3:44])[CH2:41][CH3:42])[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 11108942Carbonic acid 4-nitro-phenyl ester (R)-1-phenyl-ethyl esterHCID 66674012trans-7-Amino-8,8-diethyl-6-methoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid amide hydrochloride

Product 1

HCID 57737891((2S,3S)-7-Carbamoyl-1,1-diethyl-3-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-carbamic acid (R)-1-phenyl-ethyl esterYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of carbonic acid 4-nitro-phenyl ester (R)-1-phenyl-ethyl ester (102 g, 357 mmol), N,N-dimethylformamide (200 mL) and triethylamine (32.7 mL, 235 mmol) was stirred at room temperature overnight. To the reaction mixture was added trans-7-amino-8,8-diethyl-6-methoxy-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid amide hydrochloride (100 g, 320 mmol), N,N-dimethylformamide (320 mL) and triethylamine (98.0 mL, 703 mmol). The reaction mixture was heated at 85° C. for 5 h and then stirred at room temperature overnight. Approximately 90% of the DMF was removed by distillation at 70° C. and the resulting thick oil was cooled to room temperature and then partitioned between ethyl acetate (1.5 L) and diluted brine (500 mL). The organic layer was washed with 1M NaOH (3×500 mL) and dried with Na2SO4. Most of the solvent was removed by rotary evaporation, 3 volumes ethyl acetate were added and resulting slurry was stirred at room temperature for 30 min, filtered and dried to give the title compound (48 g, >99% chemical and optical purity).

Workup

  1. temperatureThe reaction mixture was heated at 85° C. for 5 h
  2. stirringstirred at room temperature overnight
  3. customApproximately 90% of the DMF was removed by distillation at 70° C.
  4. temperaturethe resulting thick oil was cooled to room temperature
  5. custompartitioned between ethyl acetate (1.5 L) and diluted brine (500 mL)
  6. washThe organic layer was washed with 1M NaOH (3×500 mL)
  7. dry with materialdried with Na2SO4
  8. customMost of the solvent was removed by rotary evaporation, 3 volumes ethyl acetate
  9. additionwere added
  10. customresulting slurry
  11. stirringwas stirred at room temperature for 30 min
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-af393cd2c63c4322b33741e9c1b67bdd
Source dataset
uspto-grants-2014_04
Patent number
US08703791B2

Reaction notes

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