Water → (R)-[4-({bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamoyl}-methoxy)-phenyl]-tert-butoxycarbonylamino-acetic acid

HRID 227156Notes

Reaction equation

HRID 227156 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[C:22]([Si:26]([CH3:46])([CH3:45])[O:27][CH2:28][CH2:29][N:30]([CH2:35][CH2:36][O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[C:31](=[O:34])[CH2:32]Cl)([CH3:25])([CH3:24])[CH3:23].O>CN(C)C=O>[C:41]([Si:38]([CH3:40])([CH3:39])[O:37][CH2:36][CH2:35][N:30]([CH2:29][CH2:28][O:27][Si:26]([CH3:45])([CH3:46])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:31]([CH2:32][O:19][C:16]1[CH:17]=[CH:18][C:13]([C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:10]([OH:12])=[O:11])=[CH:14][CH:15]=1)=[O:34])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 11821572Boc-4-hydroxy-D-phenylglycineHCID 15287415N,N-bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-chloro-acetamide2×

Product 1

HCID 66815288(R)-[4-({bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamoyl}-methoxy)-phenyl]-tert-butoxycarbonylamino-acetic acidYield 91.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
10 °C

Procedure

(R)-tert-Butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (1.0 g, 3.741 mmol) was dissolved dry N,N-dimethylformamide (10 mL) and cooled in an ice bath. To this was added portionwise a 60% dispersion of sodium hydride in mineral oil (344 mg, 8.604 mmol). The mixture was then warmed to 10° C. for 0.5 hours, then cooled in an ice bath and N,N-bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-chloro-acetamide (2.13 g, 4.67 mmol) added slowly in dry N,N-dimethylformamide (5 mL). The reaction mixture was warmed to ambient temperature and stirred overnight. Analysis of the reaction mixture by 1H NMR indicated 75% conversion to product. The reaction mixture was cooled in an ice bath and a 60% dispersion of sodium hydride in mineral oil (68 mg, 0.748 mmol) added. After a few minutes N,N-bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-chloro-acetamide (0.46 g, 0.426 mmol) was added. The reaction mixture was warmed to ambient temperature over 1 hour. The reaction mixture was then poured into water (50 mL) and extracted with diethyl ether (2×50 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL). The organic solution was dried over sodium sulfate, filtered and concentrated in vacuo to give (R)-[4-({bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-carbamoyl}-methoxy)-phenyl]-tert-butoxycarbonylamino-acetic acid (2.2 g, 45.9%) which was used in step 14-E without further purification.

Workup

  1. temperaturecooled in an ice bath
  2. temperaturecooled in an ice bath
  3. temperatureThe reaction mixture was warmed to ambient temperature
  4. temperatureThe reaction mixture was cooled in an ice bath
  5. temperatureThe reaction mixture was warmed to ambient temperature over 1 hour
  6. extractionextracted with diethyl ether (2×50 mL)
  7. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  8. dry with materialThe organic solution was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-39881b9307414738ab4c24ae16b59fac
Source dataset
uspto-grants-2009_07
Patent number
US07557221B2

Reaction notes

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