Acetic Anhydride → HCID 68558939, compound

HRID 20366Notes

Reaction equation

HRID 20366 reaction equation
C(N(CC)CC)C.[C:8](OC(=O)C)(=[O:10])[CH3:9].[C:15]([O:19][C:20]([N:22]1[C@@H:27]([C@@H:28]([OH:40])[C@@H:29]([NH2:39])[CH2:30][C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[C:33]([F:38])[CH:32]=2)[CH2:26][O:25][C@@H:24]([CH2:41][CH2:42][CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>O1CCCC1.ClCCl>[C:15]([O:19][C:20]([N:22]1[C@@H:27]([C@@H:28]([OH:40])[C@@H:29]([NH:39][C:8](=[O:10])[CH3:9])[CH2:30][C:31]2[CH:32]=[C:33]([F:38])[CH:34]=[C:35]([F:37])[CH:36]=2)[CH2:26][O:25][C@@H:24]([CH2:41][CH2:42][CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 685607005-(R)-[2-(S)-Amino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(2-cyclohexylethyl)-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68558939HCID 68558939, compoundYield 37.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add triethylamine (0.04 mL, 0.32 mmol) followed by acetic anhydride (0.03 mL, 0.32 mmol) to a solution of 5-(R)-[2-(S)-amino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(2-cyclohexylethyl)-morpholine-4-carboxylic acid tert-butyl ester (138 mg, 0.29 mmol) in dry tetrahydrofuran (3 mL). Stir at room temperature for 10 min. Dilute with dichloromethane, wash with 0.1 N hydrochloric acid (30 mL), dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 45:55 to 70:30 ethyl acetate:dichloromethane) to give the title compound (57 mg).

Workup

  1. washwash with 0.1 N hydrochloric acid (30 mL)
  2. dry with materialdry (sodium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 45:55 to 70:30 ethyl acetate:dichloromethane)

Sources & evidence

ORD record
ord-fb5feefd10d34a2c866825b9e1cb4845
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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