Methyl 2-bromopropionate → HCID 86701757, compound

HRID 2174113Notes

Reaction equation

HRID 2174113 reaction equation
[C:1]([C:3]1[CH:39]=[CH:38][C:6]2[N:7]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:8]([CH2:10][C:11]3[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH3:22])=[C:16]4[C:12]=3[CH:13]=[CH:14][N:15]4[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[N:9][C:5]=2[CH:4]=1)#[N:2].[C:40]([C:42]1[CH:43]=[CH:44][C:45]2[N:49]=[C:48]([CH2:50][C:51]3[C:59]([O:60][CH3:61])=[CH:58][C:57]([CH3:62])=[C:56]4[C:52]=3[CH:53]=[CH:54][N:55]4[C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[N:47]([CH2:70][O:71][CH2:72][CH2:73][Si:74]([CH3:77])([CH3:76])[CH3:75])[C:46]=2[CH:78]=1)#[N:41].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH:90]([CH3:95])[C:91]([O:93][CH3:94])=[O:92].C([O-])(O)=O.[Na+]>C1COCC1>[C:1]([C:3]1[CH:39]=[CH:38][C:6]2[N:7]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:36])([CH3:37])[CH3:35])[C:8]([CH:10]([C:11]3[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH3:22])=[C:16]4[C:12]=3[CH:13]=[CH:14][N:15]4[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH:90]([CH3:95])[C:91]([O:93][CH3:94])=[O:92])=[N:9][C:5]=2[CH:4]=1)#[N:2].[C:40]([C:42]1[CH:43]=[CH:44][C:45]2[N:49]=[C:48]([CH:50]([C:51]3[C:59]([O:60][CH3:61])=[CH:58][C:57]([CH3:62])=[C:56]4[C:52]=3[CH:53]=[CH:54][N:55]4[C:63]([O:65][C:66]([CH3:67])([CH3:68])[CH3:69])=[O:64])[CH:90]([CH3:95])[C:91]([O:93][CH3:94])=[O:92])[N:47]([CH2:70][O:71][CH2:72][CH2:73][Si:74]([CH3:76])([CH3:77])[CH3:75])[C:46]=2[CH:78]=1)#[N:41]

Participants

8

Reactant 5

HCID 95576Methyl 2-bromopropionateHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 86701791HCID 86701791, compoundHCID 86701792HCID 86701792, compound

Product 2

HCID 86701757HCID 86701757, compoundHCID 86701758HCID 86701758, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To tert-Butyl 4-((5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and tert-butyl 4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 145-A) (850 mg, 1.55 mmol) in THF (20 mL) at −78° C. was added 1 M LHMDS in THF (4.6 mL, 4.6 mmol) and the reaction was stirred for 30 minutes. Methyl 2-bromopropanoate (1.72 mL, 15.5 mmol) was then added and the reaction was allowed to stir at room temperature for 2 hours. The mixture was poured into a saturated aq. solution of NaHCO3 (80 mL) and extracted with ethyl acetate, dried over sodium sulfate, concentrated, and purified via preparative HPLC(X-terra MS, C18 column, 20 mL/min) to obtain (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate as a single diastereomer (diastereomer A, tr=16.9 min) and (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-2-methyl-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate as a single diastereomer (diastereomer B, tr=18.7 min). MS (ESI+) m/z 633.2 (M+H).

Workup

  1. stirringto stir at room temperature for 2 hours
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified via preparative HPLC(X-terra MS, C18 column, 20 mL/min)

Sources & evidence

ORD record
ord-d65937ceffee4ad3aeda8b2a0d4c4bc5
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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