Ammonium Chloride → (2S)-tert-butyl 2-(4-carbamoylphenyl)morpholine-4-carboxylate

HRID 2063347Notes

Reaction equation

HRID 2063347 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C([N:26]=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>CN(C)C=O>[C:18]([C:17]1[CH:21]=[CH:22][C:14]([C@@H:10]2[O:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]2)=[CH:15][CH:16]=1)(=[O:19])[NH2:26]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 668420684-(1,1-Dimethylethyl) (2S)-2-(4-carboxyphenyl)-4-morpholinecarboxylate2×

Product 1

HCID 58097883(2S)-tert-butyl 2-(4-carbamoylphenyl)morpholine-4-carboxylateYield 93.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2S)-4-(tert-butoxycarbonyl)morpholin-2-yl)benzoic acid (intermediate 16, 22.4 g, 72.9 mmol) in N,N-dimethylformamide (185 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (21.0 g, 109 mmol), 1-hydroxybenzotriazole hydrate (16.8 g, 109 mmol), N,N diisopropylethylamine (37.7 g, 292 mmol) and ammonium chloride (7.80 g, 146 mmol) at room temperature. After stirring for 6 hours the mixture was partitioned between water and ethyl acetate, and the organic layer was washed with water and brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure to afford (2S)-tert-butyl 2-(4-carbamoylphenyl)morpholine-4-carboxylate (intermediate 17, 20.9 g, 93%).

Workup

  1. customwas partitioned between water and ethyl acetate
  2. washthe organic layer was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-f0ec24197a0d4e52af3607434a8ea072
Source dataset
uspto-grants-2012_10
Patent number
US08288383B2

Reaction notes

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