Methyl chloroformate → HCID 86726362, compound

HRID 629758Notes

Reaction equation

HRID 629758 reaction equation
[NH2:1][C@@H:2]([C@@H:38]([C:47]1[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=1)[C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([F:46])[CH:40]=1)[C:3]([NH:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([F:37])[C:11]=1[CH2:12][CH2:13][C@H:14]1[O:19][CH2:18][C@H:17]([CH2:20][O:21][C:22]([NH:24][CH2:25][C:26]([F:29])([F:28])[F:27])=[O:23])[N:16]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:15]1)=[O:4].C(N(CC)CC)C.Cl[C:62]([O:64][CH3:65])=[O:63]>C(Cl)Cl>[CH3:65][O:64][C:62]([NH:1][C@@H:2]([C@@H:38]([C:47]1[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=1)[C:39]1[CH:40]=[C:41]([F:46])[CH:42]=[C:43]([F:45])[CH:44]=1)[C:3]([NH:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([F:37])[C:11]=1[CH2:12][CH2:13][C@H:14]1[O:19][CH2:18][C@H:17]([CH2:20][O:21][C:22]([NH:24][CH2:25][C:26]([F:29])([F:27])[F:28])=[O:23])[N:16]([C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[CH2:15]1)=[O:4])=[O:63]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 86726360HCID 86726360, compound

Product 1

HCID 86726362HCID 86726362, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (2S,3S)-2-amino-3-(4-fluorophenyl)-3-(3,5-difluorophenyl)-N-(5-fluoro-4-(2-((2R,5R)-4-(tert-butyloxycarbonyl)-5-(2,2,2-trifluoroethylaminocarbonyloxymethyl)morpholine-2-yl)ethyl)pyridin-3-yl)propanamide (Example 90, step 5) (64 mg, 0.084 mmol) in 1 mL of CH2Cl2 was added triethylamine (0.047 mL, 0.34 mmol) and methyl chloroformate (0.013 mL, 0.17 mmol). The mixture was stirred at ambient temperature for 1 h, then diluted with CH2Cl2 and washed with aqueous NaHCO3 and brine. The organic phase was dried (MgSO4), filtered, and the solvents were removed in vacuo. The residue was chromatographed on a 12 g SiO2 column using a gradient elution of 0-100% EtOc in hexanes. Fractions containing product were combined and the solvents were removed in vacuo to give a gum. LC MS: RT=1.38 min, M+H=816 (2 min gradient)

Workup

  1. washwashed with aqueous NaHCO3 and brine
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. customthe solvents were removed in vacuo
  5. customThe residue was chromatographed on a 12 g SiO2 column
  6. washa gradient elution of 0-100% EtOc in hexanes
  7. additionFractions containing product
  8. customthe solvents were removed in vacuo
  9. customto give a gum
  10. customRT=1.38 min, M+H=816 (2 min gradient)

Sources & evidence

ORD record
ord-66a34173e4f34672a59c8af2511da6fc
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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