tert-Butyldimethylsilyl chloride → (2S,4R)-1-allyloxycarbonyl-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine

HRID 1826105Notes

Reaction equation

HRID 1826105 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([OH:12])[CH2:9][C@H:8]1[CH2:13][OH:14])=[O:6])[CH:2]=[CH2:3].[CH3:15][C:16]([Si:19](Cl)([CH3:21])[CH3:20])([CH3:18])[CH3:17].C1CCN2C(=NCCC2)CC1>C(Cl)Cl.CCOC(C)=O>[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([OH:12])[CH2:9][C@H:8]1[CH2:13][O:14][Si:19]([C:16]([CH3:18])([CH3:17])[CH3:15])([CH3:21])[CH3:20])=[O:6])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 28928tert-Butyldimethylsilyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15086219(2S,4R)-1-allyloxycarbonyl-4-hydroxy-2-hydroxymethylpyrrolidine

Product 1

HCID 18639173(2S,4R)-1-allyloxycarbonyl-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the diol 14 (16.97 g, 84 mmol) in CH2Cl2 (235 mL) was treated with TEA (11.7 mL, 8.5 g, 84 mmol) and stirred for 15 minutes at room temperature. TBDMSCl (9.72 g, 64 mmol) and DBU (16.8 mmol, 2.51 mL, 2.56 g) were added and the reaction mixture stirred for a further 16 hours under a nitrogen atmosphere. The reaction mixture was diluted with EtOAc (500 mL), washed with saturated NH4Cl (160 mL), brine (160 mL), dried (MgSO4), filtered and evaporated in vacuo to give an oil which was a mixture of the required product (major component), unreacted diol and the presumed disilyated compound by TLC (50% EtOAc/Petroleum Ether). Flash chromatography (20-100% EtOAc/Petroleum Ether) isolated the 3 components, to provide the monosilylated compound 15 as a slightly yellow transparent oil (13.85 g, 52%): [α]21D=−58.6° (c=1.14, CHCl3); 1H NMR (270 MHz, CDCl3) (Rotamers) δ 6.01-5.86 (m, 1H, NCO2CH2CH═CH2), 5.34-5.18 (m, 2H, NCO2CH2CH═CH2), 4.59-4.49 (m, 3H, NCO2CH2CH═CH2 and NCHCH2OTBDMS), 4.06-3.50 (m, 5H, NCH2CHOH, NCH2CHOH and NCHCH2OTBDMS), 2.20-2.01 (m, 2H, NCH2CHOHCH2), 0.87 (s, 9H, SiC(C3)2), 0.0 (s, 6H, Si(CH3)2); 13C NMR (67.8 MHz, CDCl3) (Rotamers) δ 155.0 (NC═O), 133.1 (NCO2CH2CH═CH2), 117.6 and 117.1 (NCO2CH2CH═CH2), 70.3 and 69.7 (NCH2CHOH), 65.9 and 65.6 (NCO2CH2CH═CH2), 63.9 and 62.8 (NCHCH2OTBDMS), 57.8 and 57.4 (NCHCH2OTBDMS), 55.7 and 55.2 (NCH2CHOH), 37.3 and 36.6 (NCH2CHOHCH2), 25.9 (SiC(CH2)2), 18.2 (SiC(CH3)3), −5.5 (Si(CH3)2); MS (EI), m/z (relative intensity) 316 (M+.+1, 29), 315 (M+., 4), 300 (M-CH3, 26), 284 (4), 261 (8), 260 (50), 259 (100), 258 (M-OC3H3 or M-tBu, 100), 218 (13), 215 (10), 214 (52), 200 (12), 170 (M-CH2OTBDMS, 100), 156 (40), 126 (58), 115 (33), 108 (41), 75 (35); IR (Neat) 3422 (br, OH), 2954, 2858, 1682 (C═O), 1467, 1434, 1412 (SiCH2), 1358, 1330, 1255 (SiCH2) 1196, 1180, 1120, 1054, 995, 919, 837, 776, 669 cm−1; exact mass calcd for C15H29NO4Si m/e 315.1866, obsd m/e 315.1946.

Workup

  1. stirringthe reaction mixture stirred for a further 16 hours under a nitrogen atmosphere
  2. washwashed with saturated NH4Cl (160 mL), brine (160 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto give an oil which

Sources & evidence

ORD record
ord-99e4db2b02e349638f54bcb86525b974
Source dataset
uspto-grants-2006_05
Patent number
US07049311B1

Reaction notes

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