Chlorotrimethylsilane → (2S,3S)-2-{(R)-2-amino-2-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide

HRID 1433786

Reaction equation

HRID 1433786 reaction equation
[NH2:1][C@H:2]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][C@H:34]([OH:37])[CH2:35][OH:36])=[CH:28][CH:27]=1)[C:3]([NH:5][C@@H:6]([C@H:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:19])[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=1[Cl:17])=[O:8])=[O:4].C(N(CC)CC)C.Cl[Si:46]([CH3:49])([CH3:48])[CH3:47]>C(OCC)(=O)C>[NH2:1][C@H:2]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][C@H:34]([O:37][Si:46]([CH3:49])([CH3:48])[CH3:47])[CH2:35][O:36][Si:46]([CH3:49])([CH3:48])[CH3:47])=[CH:28][CH:27]=1)[C:3]([NH:5][C@@H:6]([C@H:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:19])[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=1[Cl:17])=[O:8])=[O:4]

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 69006543(2S,3S)-2-{(R)-2-amino-2-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide

Product 1

HCID 69007900(2S,3S)-2-{(R)-2-amino-2-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S,3S)-2-{(R)-2-amino-2-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide (330 mg, 0.44 mmol) in dry, degassed tetrahydrofuran (5 mL) were added triethylamine (277 μL, 1.98 mmol) and chlorotrimethylsilane (230 μL, 1.76 mmol) and the mixture stirred at ambient temperature for 30 minutes. The resulting suspension was diluted with ethyl acetate (50 mL) and washed with brine (2×50 mL). The combined brine layers were back extracted with ethyl acetate (2×50 mL), the combined organic layers dried over sodium sulfate, filtered and concentrated in vacuo to give crude (2S,3S)-2-{(R)-2-amino-2-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide which was of adequate purity for subsequent use in step 6 without additional purification (330 mg, 96%).

Workup

  1. customdegassed tetrahydrofuran (5 mL)
  2. washwashed with brine (2×50 mL)
  3. extractionThe combined brine layers were back extracted with ethyl acetate (2×50 mL)
  4. dry with materialthe combined organic layers dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6932d8c887654d449c7c94041be1265e
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Linked notes

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