Hydrochloric Acid → 6-{4-(4-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-6-hydroxymethyl-tetrahydro-furo(3,4-d)(1,3)dioxol-2-yl)-phenoxy}-hexanoic acid

HRID 1797384Notes

Reaction equation

HRID 1797384 reaction equation
[OH-].[Na+].C([O:5][C:6](=[O:37])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[O:23][CH:22]3[CH:24]([CH2:35][OH:36])[O:25][CH:26]([N:27]4[CH:32]=[CH:31][C:30](=[O:33])[NH:29][C:28]4=[O:34])[CH:21]3[O:20]2)=[CH:15][CH:14]=1)C.Cl>O.CO>[O:34]=[C:28]1[NH:29][C:30](=[O:33])[CH:31]=[CH:32][N:27]1[CH:26]1[CH:21]2[CH:22]([O:23][CH:19]([C:16]3[CH:15]=[CH:14][C:13]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]([OH:37])=[O:5])=[CH:18][CH:17]=3)[O:20]2)[CH:24]([CH2:35][OH:36])[O:25]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 695881876-{4-(4-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-6-hydroxymethyl-tetrahydro-furo(3,4-d)(1,3)dioxol-2-yl)-phenoxy}-hexanoic acid ethyl ester

Product 1

HCID 221776446-{4-(4-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-6-hydroxymethyl-tetrahydro-furo(3,4-d)(1,3)dioxol-2-yl)-phenoxy}-hexanoic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of NaOH (12.6 g, 315 mmol) in H2O (100 mL) was added to a suspension of 6 (50 g, 102 mmol) in MeOH (750 mL) and stirred for 8 h at room temperature. Approximately half of the solvent was removed in vacuo and the remainder was treated dropwise with 1 M aqueous HCl (315 mmol, 315 mL). The white precipitate was filtered, washed with H2O (2×200 mL) and Et2O (3×200 mL) and dried in vacuo to afford a white powder (15, 46.7 g, 100 mmol, 99%) as a mixture of two diastereomers: M.p.: 158-160° C.; 1H-NMR (400 MHz, (CD3)2SO3) δ=11.95 (s, 1H, 1H′), 11.38 (s, 1H, 1H′), 7.85 (d, J=8.0, 1H), 7.77 (d, J=8.0, 1H′), 7.41 (d, J=8.5, 2H), 7.37 (d, J=8.5, 2H′), 6.96 (d, J=8.5, 2H), 6.93 (d, J=8.5, 2H′), 6.04 (s, 1H′), 5.93 (m, 1H, 1H′), 5.90 (s, 1H), 5.64 (d, J=8.0, 1H), 5.63 (d, J=8.0, 1H′), 5.2 (broad, 1H, 1H′), 4.99-4.83 (m, 2H, 2H′), 4.23 (m, 1H), 4.13 (m, 1H′), 3.97 (m, 2H, 2H′), 3.62 (m, 2H, 2H′), 2.20 (m, 2H, 2H′), 1.70 (m, 2H, 2H′, 1.54 (m, 2H, 2H′), 1.41 (m, 2H, 2H′); 13C -NMR (400 MHz, (CD3)2SO3) δ=176.0, 176.0, 164.1, 164.1, 160.6, 160.5, 151.2, 151.2, 143.0, 143.0, 129.3 (2C), 129.3 (2C), 128.9, 128.9, 115.1 (2C), 115.0 (2C), 107.4, 103.4, 102.8, 102.6, 92.2, 91.3, 87.3, 85.1, 84.8, 83.7, 82.6, 80.8, 68.3, 68.3, 62.2, 62.2, 35.1, 35.1, 29.3, 29.3, 26.1, 26.1, 25.4, 25.4; IR (film) ν=3467, 3132, 2938, 1696, 1677, 1245, 1108, 1077, 1046, 1019, 976, 828, 809; HRMS (MALDI-FTMS) m/z 485.1534 (485.1536 calculated for C22H26N2O9Na (M+Na)+).

Workup

  1. customApproximately half of the solvent was removed in vacuo
  2. filtrationThe white precipitate was filtered
  3. washwashed with H2O (2×200 mL) and Et2O (3×200 mL)
  4. customdried in vacuo
  5. customto afford a white powder (15, 46.7 g, 100 mmol, 99%)
  6. additionas a mixture of two diastereomers

Sources & evidence

ORD record
ord-7de7fddecade4294b71c357c827b07a1
Source dataset
uspto-grants-2006_04
Patent number
US07034147B2

Reaction notes

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