Sodium triacetoxyborohydride → HCID 58305954, compound

HRID 1844316Notes

Reaction equation

HRID 1844316 reaction equation
[NH2:1][C@H:2]1[CH2:6][C@@:5]([C:17]2([OH:21])[CH2:20][CH2:19][CH2:18]2)([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH:4]=[CH:3]1.[CH3:22][O:23][C@H:24]1[C:29](=O)[CH2:28][CH2:27][O:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].[OH-].[Na+]>ClCCl>[CH2:10]([O:9][C:7]([C@:5]1([C:17]2([OH:21])[CH2:18][CH2:19][CH2:20]2)[CH2:6][C@H:2]([NH:1][C@@H:29]2[C@H:24]([O:23][CH3:22])[CH2:25][O:26][CH2:27][CH2:28]2)[CH:3]=[CH:4]1)=[O:8])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 11320949(R)-3-methoxydihydro-2H-pyran-4(3H)-oneHCID 58305932HCID 58305932, compoundHCID 129628726Soda-Natronlauge

Product 1

HCID 58305954HCID 58305954, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3.83 g (13.3 mmol) of benzyl (1R,4S)-4-amino-1-(1-hydroxycyclobutyl)cyclopent-2-ene-1-carboxylate (Preparation SRT-0235) and 1.89 g (14.5 mmol) of (3R)-3-methoxytetrahydro-4H-pyran-4-one in 26 mL of dichloromethane was stirred with activated 3 A molecular sieves for 10 min, then cooled to 0 C. Sodium triacetoxyborohydride (3.35 g, 15.8 mmol) was added in several portions ever 10 min, and the mixture was stirred for 1.5 h. The cloudy mixture was added to dichloromethane and aqueous NaHCO3+NaOH (pH ˜14), and the aqueous phase was extracted with several additional portions of dichloromethane. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography of the residue on silica using 3-5% methanolic ammonia (7 M) in dichloromethane afforded 3.94 g (74%) of the title compound as a yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.41-1.52 (m, 1H) 1.55-1.64 (m, 1H) 1.64-1.79 (m, 2H) 1.86-2.09 (m, 5H) 2.19-2.29 (m, 1H) 2.41 (dd, J=14.2, 7.7 Hz, 1H) 2.84-2.91 (m, 1H) 3.17-3.44 (m, 4H) 3.34 (s, 3H) 3.88-3.96 (m, 2H) 4.00 (dd, J=12.3, 4.4 Hz, 1H) 5.10-5.20 (m, 2H) 5.88-5.93 (m, 1H) 6.00 (dd, J=5.6, 1.9 Hz, 1H) 7.28-7.39 (m, 5H). TLC Rf 0.41 (4% 7 M methanolic ammonia in dichloromethane). LC-MS ES+ 402.1.

Workup

  1. temperaturecooled to 0 C
  2. extractionthe aqueous phase was extracted with several additional portions of dichloromethane
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-34607b1881504ef0842d334c78540b05
Source dataset
uspto-grants-2015_02
Patent number
US08946413B2

Reaction notes

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