Sodium hydride → HCID 59396023, compound

HRID 1094751Notes

Reaction equation

HRID 1094751 reaction equation
[CH3:1][C:2]([Si:5]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[O:6][CH2:7][C@@H:8]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:9][CH:10]1[CH2:12][CH:11]1[CH2:13]O)([CH3:4])[CH3:3].S(Cl)(C)(=O)=O.[H-].[Na+]>C(Cl)Cl.CN(C=O)C>[CH3:3][C:2]([Si:5]([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[O:6][CH2:7][C@@H:8]1[CH2:9][C@H:10]2[C@H:11]([CH2:12]2)[CH2:13][N:15]1[C:16]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:25])([CH3:4])[CH3:1]

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 31297Methanesulfonyl chlorideHCID 59396021HCID 59396021, compound

Product 1

HCID 59396023HCID 59396023, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To an ice cooled solution of phenylmethyl ((1S)-2-{[(1,1 dimethylethyl)(diphenyl)silyl]oxy}-1-{[2-(hydroxymethyl)cyclopropyl]methyl}ethyl)carbamate single diastereoisomer 1 D7 (1.18 g) in DCM (35 ml) and TEA (0.953 ml, 6.84 mmol) was added mesyl chloride (0.355 ml, 4.56 mmol) and the resulting mixture was stirred for 3 hours. After this time the solvent was removed under reduced pressure and the white solid obtained was dissolved in DMF (47 ml), the solution was cooled to 0° C. and NaH (0.730 g, 18.25 mmol, 8 eq) was added and ice bath was removed. After stirring overnight more NaH (0.365 g, 9.12 mmol, 4 eq) was added to the ice cooled mixture and stirred at room temperature for 3 hours. UPLC showed starting material and desired product in 1:1 ratio, so NaH (0.180 g, 4.5 mmol, 1.97 eq) was added at room temperature and stirred for 2.5 hours. A saturated solution of NH4Cl (300 ml) was added and extracted with EtOAc (3×50 mls), the organic phase was separated, dried (Na2SO4), filtered and evaporated to give a yellow oil which was purified via Biotage SP4 (silica gel, SNAP 100 g column; eluted with a gradient of Cy/EtOAc from 1/0 to 9/1). Collected fractions gave the title compound D8 (0.930 g) as a colourless oil. MS: (ES/+) m/z: 500 (M+1). C31H37NO3Si requires 499. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.76-7.31 (m, 15 H), 5.16-4.84 (m, 2 H), 4.37 (br.s, 1 H), 3.83-3.68 (m, 1 H), 3.68-3.52 (m, 2 H), 2.37-2.22 (m, 2 H), 1.39-1.18 (m, 1 H), 1.13-1.01 (m, 1 H), 0.95 (s, 9 H), 0.92-0.83 (m, 1 H), 0.79-0.70 (m, 1 H), 0.33-0.04 (m, 1 H).

Workup

  1. customAfter this time the solvent was removed under reduced pressure
  2. customthe white solid obtained
  3. customice bath was removed
  4. temperaturecooled mixture
  5. stirringstirred at room temperature for 3 hours

Sources & evidence

ORD record
ord-2fb99b3b4d2b4ac38235b3609d22ae97
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

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