Diethylamine → (2S)-2-Amino-3-(4-(benzyloxy)-2-fluorophenyl)-N-(2,2-diethoxyethyl)-N-((6-fluoropyridin-2-yl)methyl)propanamide

HRID 707493Notes

Reaction equation

HRID 707493 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@H:16]([NH:36]C(=O)OCC2C3C=CC=CC=3C3C2=CC=CC=3)[C:17](=[O:35])[N:18]([CH2:27][CH:28]([O:32][CH2:33][CH3:34])[O:29][CH2:30][CH3:31])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[N:21]=2)=[C:11]([F:54])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1COCC1.C(NCC)C>C(OCC)(=O)C>[NH2:36][C@@H:16]([CH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][C:11]=1[F:54])[C:17]([N:18]([CH2:27][CH:28]([O:32][CH2:33][CH3:34])[O:29][CH2:30][CH3:31])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[N:21]=1)=[O:35]

Participants

5

Reactant 3

HCID 8021DiethylamineHCID 8028TetrahydrofuranHCID 1181624199H-fluoren-9-ylmethyl N-((1S)-2-(4-(benzyloxy)-2-fluorophenyl)-1-((2,2-diethoxyethyl)((6-fluoropyridin-2-yl)methyl)carbamoyl)ethyl)carbamate

Product 1

HCID 118162542(2S)-2-Amino-3-(4-(benzyloxy)-2-fluorophenyl)-N-(2,2-diethoxyethyl)-N-((6-fluoropyridin-2-yl)methyl)propanamideYield 93%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixed solution of 9H-fluoren-9-ylmethyl N-((1S)-2-(4-(benzyloxy)-2-fluorophenyl)-1-((2,2-diethoxyethyl)((6-fluoropyridin-2-yl)methyl)carbamoyl)ethyl)carbamate described in Production Example 1-1-2 (14.4 g) and THF (30 mL) was added diethylamine (5.27 mL, 50.4 mmol) at room temperature. The resultant mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under a reduced pressure, methanol, water and heptane were added to the residue, and the resultant mixture was partitioned. An aqueous layer was washed with heptane, and was then concentrated under a reduced pressure. Water was added to the residue, and the resultant solution was extracted with ethyl acetate. An organic layer was dried over anhydrous magnesium sulfate and then filtrated. The solvent was evaporated under a reduced pressure, and the resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1, and then ethyl acetate) to give the title compound (6.87 g, yield: 93%).

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure, methanol, water and heptane
  2. additionwere added to the residue
  3. customthe resultant mixture was partitioned
  4. washAn aqueous layer was washed with heptane
  5. concentrationwas then concentrated under a reduced pressure
  6. additionWater was added to the residue
  7. extractionthe resultant solution was extracted with ethyl acetate
  8. dry with materialAn organic layer was dried over anhydrous magnesium sulfate
  9. filtrationfiltrated
  10. customThe solvent was evaporated under a reduced pressure
  11. customthe resultant residue was purified by NH silica gel column chromatography (heptane

Sources & evidence

ORD record
ord-e6746a13b80d4b618e9b5849089d7ba7
Source dataset
uspto-grants-2015_11
Patent number
US09174998B2

Reaction notes

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